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Focal adhesion-derived liquid-liquid phase separations regulate mRNA translation bioRxiv. Cell Biol. Pub Date : 2024-04-18 Abhishek Kumar, Keiichiro Tanaka, Martin A Schwartz
Liquid-liquid phase separation (LLPS) has emerged as a major organizing principle in cells. Recent work showed that multiple components of integrin-mediated focal adhesions including p130Cas can form LLPS, which govern adhesion dynamics and related cell behaviors. In this study, we found that the focal adhesion protein p130Cas drives formation of structures with the characteristics of LLPS that bud
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Mechanotransductive feedback control of endothelial cell motility and vascular morphogenesis bioRxiv. Cell Biol. Pub Date : 2024-04-18 Devon E Mason, Paula Camacho, Megan Goeckel, Brendan R Tobin, Sebastian L Vega, Pei-Hsun Wu, Dymonn Johnson, Su-Jin Heo, Denis Wirtz, Jason A Burdick, Levi Wood, Brain Y Chow, Amber N Stratman, Joel D Boerckel
Vascular morphogenesis requires persistent endothelial cell motility that is responsive to diverse and dynamic mechanical stimuli. Here, we interrogated the mechanotransductive feedback dynamics that govern endothelial cell motility and vascular morphogenesis. We show that the transcriptional regulators, YAP and TAZ, are activated by mechanical cues to transcriptionally limit cytoskeletal and focal
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Viscoelastic Extracellular Matrix Enhances Epigenetic Remodeling and Cellular Plasticity bioRxiv. Cell Biol. Pub Date : 2024-04-17 Yifan Wu, Yang Song, Jennifer Soto, Tyler Hoffman, Aaron Zhang, Xiao Han, Zhiwei Fang, Joon Eoh, Luo Gu, Zhen Gu, Song Li
Living tissue and extracellular matrices possess viscoelastic properties, but understanding how viscoelastic matrix regulates chromatin and the epigenome is limited. Here, we find that the regulation of the epigenetic state by the viscoelastic matrix is more pronounced on softer matrices. Cells on viscoelastic matrices exhibit larger nuclei, increased nuclear lamina ruffling, loosely organized chromatin
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A MSTNDel273C mutation with FGF5 knockout sheep by CRISPR/Cas9 promotes skeletal muscle myofiber hyperplasia bioRxiv. Cell Biol. Pub Date : 2024-04-17 Mingming Chen, Yue Zhao, Xueling Xu, Xiaosheng Zhang, Jinlong Zhang, Sujun Wu, Zhimei Liu, Yiming Yuan, Xiaofei Guo, Shiyu Qi, Guang Yi, Shuqi Wang, Huangxiang Li, Aowu Wu, Guoshi Liu, Kun Yu, Shoulong Deng, Hongbing Han, Fenghua Lv, Yan Li, Zhengxing Lian
Mutations in the well-known Myostatin (MSTN) produce a "double-muscle" phenotype, which makes it commercially invaluable for improving livestock meat production and providing high-quality protein for humans. However, mutations at different loci of the MSTN often produce a variety of different phenotypes. In the current study, we increased the delivery ratio of Cas9 mRNA to sgRNA from the traditional
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Editing of endogenous tubulins reveals varying effects of tubulin posttranslational modifications on axonal growth and regeneration bioRxiv. Cell Biol. Pub Date : 2024-04-17 Yu-Ming Lu, Shan Yan, Shih-Chieh Ti, Chaogu Zheng
Tubulin posttranslational modifications (PTMs) modulate the dynamic properties of microtubules and their interactions with other proteins. However, the effects of tubulin PTMs were often revealed indirectly through the deletion of modifying enzymes or the overexpression of tubulin mutants. In this study, we directly edited the endogenous tubulin loci to install PTM-mimicking or -disabling mutations
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Dynamic Interplay of Autophagy and Membrane Repair During Mycobacterium tuberculosis Infection bioRxiv. Cell Biol. Pub Date : 2024-04-17 Jacques Augenstreich, Anna T. Phan, Charles Nathan Selby Allen, Anushka Poddar, Lalitha Srinivasan, Volker Briken
Autophagy plays a crucial role in the host response to Mycobacterium tuberculosis (Mtb) infection, yet the dynamics and regulation of autophagy induction on mycobacterial phagosomes remain partially understood. In this study, we employed time-lapse confocal microscopy to investigate in real time the recruitment of LC3B (LC3), a key autophagy marker, to Mtb-containing vacuoles (MCVs) at the single cell
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The maternal and fetal metabolic and immune landscapes of gestational diabetes mellitus bioRxiv. Cell Biol. Pub Date : 2024-04-17 Duan Ni, Ralph Nanan
Objectives: Gestational diabetes mellitus (GDM) is the most common pregnancy-related medical complication. It is characterized by the development of hyperglycaemia during pregnancy and is known to lead to higher risk of metabolic disorders and other pathologies in both mothers and offsprings. Some studies probed the impacts of GDM, focusing on specific organs like placenta or adipose tissue, but so
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Geranylgeranylated-SCFFBXO10 Regulates Selective Outer Mitochondrial Membrane Proteostasis and Function bioRxiv. Cell Biol. Pub Date : 2024-04-16 Sameer Ahmed Bhat, Zahra Vasi, Liping Jiang, Shruthi Selvaraj, Rachel Ferguson, Anish Gudur, Hagar Ismail, Ritika Adhikari, Avantika Dhabaria, Beatrix Ueberheide, Shafi Kuchay
E3-ubiquitin ligases (E3s) are main components of the ubiquitin-proteasome system (UPS), as they determine substrate specificity in response to internal and external cues to regulate protein homeostasis. However, the regulation of membrane protein ubiquitination by E3s within distinct cell membrane compartments or organelles is not well understood. We show that FBXO10, the interchangeable component
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OrgaMeas: A pipeline that integrates all the processes of organelle image analysis bioRxiv. Cell Biol. Pub Date : 2024-04-16 Taiki Baba, Akimi Inoue, Susumu Tanimura, Kohsuke Takeda
Although image analysis has emerged as a key technology in the study of organelle dynamics, the commonly used image-processing methods, such as threshold-based segmentation and manual setting of regions of interests (ROIs), are error-prone and laborious. Here, we present a highly accurate high-throughput image analysis pipeline called OrgaMeas for measuring the morphology and dynamics of organelles
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Cell cycle-dependent mRNA localization in P-bodies bioRxiv. Cell Biol. Pub Date : 2024-04-16 Adham SAFIEDDINE, Marie-Noelle Benassy, Thomas Bonte, Floric Slimani, Oriane Pourcelot, Michel Kress, Michele Ernoult-Lange, Maite Courel, Emeline Coleno, Arthur Imbert, Antoine Laine, Annie Munier Godebert, Angelique Vinit, Corinne Blugeon, Guillaume Chevreux, Daniel Gautheret, Thomas Walter, Edouard Bertrand, Marianne Benard, Dominique Weil
Understanding the dynamics of RNA targeting to membraneless organelles is essential to disentangle their functions. Here, we investigate how P-bodies (PBs) evolve during cell cycle progression. PB purification at different cell cycle phases uncovers widespread changes in their RNA content. Importantly, these changes are partly uncoupled from cell cycle-dependent changes in RNA expression. Single molecule
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Ectopic Reconstitution of a Spine-Apparatus Like Structure Provides Insight into Mechanisms Underlying Its Formation bioRxiv. Cell Biol. Pub Date : 2024-04-16 Hanieh Falahati, Yumei Wu, Pietro De Camilli
The endoplasmic reticulum (ER) is a continuous cellular endomembrane network that displays focal specializations. Most notable examples of such specializations include the spine apparatus of neuronal dendrites, and the cisternal organelle of axonal initial segments. Both organelles exhibit stacks of smooth ER sheets with a narrow lumen and interconnected by a dense protein matrix. The actin-binding
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Transcriptome-wide mRNA condensation precedes stress granule formation and excludes stress-induced transcripts bioRxiv. Cell Biol. Pub Date : 2024-04-16 Hendrik Glauninger, Jared A.M. Bard, Caitlin J. Wong Hickernell, Edo M. Airoldi, Weihan Li, Robert H. Singer, Sneha Paul, Jingyi Fei, Tobin R. Sosnick, Edward W.J. Wallace, D. Allan Drummond
Stress-induced condensation of mRNA and proteins into stress granules is conserved across eukaryotes, yet the function, formation mechanisms, and relation to well-studied conserved transcriptional responses remain largely unresolved. Stress-induced exposure of ribosome-free mRNA following translational shutoff is thought to cause condensation by allowing new multivalent RNA-dependent interactions,
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Characterising the Modulatory Role of Ikebana in Flower-Dependent Cell Competition bioRxiv. Cell Biol. Pub Date : 2024-04-16 Mariana Marques-Reis, Andres Gutierrez-Garcia, Carlos Flores Clara, Irene Argudo, Matthias Stefan Eggel, Barbara Hauert, Catarina Bras-Pereira, Eduardo Moreno
Tissues encompass a quality control mechanism that promotes their optimal state. This mechanism, designated cell competition, is characterised by the elimination of suboptimal yet viable cells when they are near healthier cells within the same tissue compartment. This study explores Flower-dependent cell competition and introduces Ikebana as a novel player. The differential expression of the flower
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Multi-Omics after O-GlcNAc Alteration Identifies Cellular Processes Working Synergistically to Promote Aneuploidy bioRxiv. Cell Biol. Pub Date : 2024-04-16 Samuel Boyd, Dakota Robarts, Khue Nguyen, Maite Villar, Ibtihal Alghusen, Manasi Kotulkar, Aspin Denson, Halyna Fedoosyuk, Norman Lee, Stephen A. Whelan, John A. Hanover, Wagneer Dias, Ee Phie Tan, Steve McGreal, Antonio Artigues, Russell H. Swerdlow, Jeffrey Thompson, Udayan Apte, Chad Slawson
Pharmacologic or genetic manipulation of O-GlcNAcylation, an intracellular, single sugar post-translational modification, are difficult to interpret due to the pleotropic nature of O- GlcNAc and the vast signaling pathways it regulates. To address this issue, we employed either OGT (O-GlcNAc transferase), OGA (O-GlcNAcase) liver knockouts, or pharmacological inhibition of OGA coupled with multi-Omics
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Metabolically intact nuclei are fluidized by the activity of the chromatin remodeling motor BRG1 bioRxiv. Cell Biol. Pub Date : 2024-04-16 Fitzroy Byfield, Behnaz Eftekhari, Kaeli Kaymak-Loveless, Kalpana Mandal, David Li, Rebecca G Wells, Wenjun Chen, Jasna Brujic, Giulia Bergamasschi, Gijs G wuite, Alison Elise Patteson, Paul Albert Janmey
The structure and dynamics of the cell nucleus regulate nearly every facet of the cell. Changes in nuclear shape limit cell motility and gene expression. Although the nucleus is generally seen as the stiffest organelle in the cell, cells can nevertheless deform the nucleus to large strains by small mechanical stresses. Here, we show that the mechanical response of the cell nucleus exhibits active fluidization
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Analysis of the Leishmania mexicana promastigote cell cycle using imaging flow cytometry provides new insights into cell cycle flexibility and events of short duration. bioRxiv. Cell Biol. Pub Date : 2024-04-16 Jessie Howell, Sulochana Omwenga, Melanie Jimenez, Tansy C Hammarton
Promastigote Leishmania mexicana have a complex cell division cycle characterised by the ordered replication of several single-copy organelles, a prolonged S phase and rapid G2 and cytokinesis phases, accompanied by cell cycle stage-associated morphological changes. Here we exploit these morphological changes to develop a high-throughput and semi-automated imaging flow cytometry (IFC) pipeline to analyse
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Rbpj deletion in hepatic progenitor cells attenuates endothelial responses in a mouse model of cholestatic liver disease bioRxiv. Cell Biol. Pub Date : 2024-04-16 Sanghoon Lee, Lu Ren, Aditi Paranjpe, Ping Zhou, Andrew Potter, Stacey S Huppert, Soona Shin
Background and Aims: Since the role of hepatic progenitor cells (HPCs) constituting ductular reactions in pathogenesis remains ambiguous, we aimed to establish the in vivo cause-and-effect relationship between HPCs and angiogenesis, a process associated with chronic liver disease progression. We previously demonstrated that peritumoral ductules are associated with angiogenesis in liver tumors and forkhead
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Development of the ULK1-Recruiting Chimeras (ULKRECs) to enable proximity-induced and ULK1-dependent degradation of mitochondria bioRxiv. Cell Biol. Pub Date : 2024-04-15 Niyaz Zaman, Natasha Aley, Valeria Pingitore, David L Selwood, Robin Ketteler
Targeted protein degradation (TPD) has opened new opportunities to investigate signalling pathways as a research tool, and as a unique therapeutic strategy using bifunctional chimeric small molecules, with candidate molecules in clinical trials for the treatment of breast cancer and prostate cancer. Most current TPD approaches use the 26S proteasomal machinery via PROteolysis TArgeting Chimeras (PROTACs)
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Nuclear basket proteins regulate the distribution and mobility of nuclear pore complexes in budding yeast bioRxiv. Cell Biol. Pub Date : 2024-04-15 Janka Zsok, Francois Simon, Goeksu Bayrak, Luljeta Isaki, Nina Kerff, Amy Wolstenholme, Lucien E Weiss, Elisa Dultz
Nuclear pore complexes (NPCs) mediate all traffic between the nucleus and the cytoplasm and are among the most stable protein assemblies in cells. Intriguingly, budding yeast cells carry two variants of NPCs which differ in the presence or absence of the nuclear basket proteins Mlp1, Mlp2 and Pml39. The binding of these basket proteins occurs very late in NPC assembly and Mlp-positive NPCs are excluded
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The ER Thioredoxin-Related Transmembrane Protein TMX2 Controls Redox-Mediated Tethering of ER-Mitochondria Contacts (ERMCS) bioRxiv. Cell Biol. Pub Date : 2024-04-15 Junsheng Chen, Megan C Yap, Arthur Bassot, Danielle M Pascual, Tadashi Makio, Jannik Zimmermann, Heather Mast, Rakesh Bhat, Samuel G Fleury, Yuxiang Fan, Adriana Zardini Buzatto, Jack Moore, Klaus Ballanyi, Liang Li, Michael Overduin, M Joanne Lemieux, Helene Lemieux, Wen-Hann Tan, Grazia M. S. Mancini, Bruce Morgan, Paul C. Marcogliese, Thomas Simmen
Thioredoxin-related transmembrane proteins (TMX) of the endoplasmic reticulum (ER) have emerged as key regulators of ER membrane properties. Within the ER lumen, TMX proteins and other ER redox enzymes determine oxidative conditions, which control the formation of ER-mitochondria membrane contacts (ERMCS) and determine their function. ERMCS exhibit cytoplasmic redox nanodomains, derived from ER and
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Improved whole-mount immunofluorescence protocol for consistent and robust labeling of adult Drosophila melanogaster adipose tissue bioRxiv. Cell Biol. Pub Date : 2024-04-15 Rachael K Ott, Alissa Richmond Armstrong
Energy storage and endocrine functions of the Drosophila fat body make it an excellent model for elucidating mechanisms that underlie physiological and pathophysiological organismal metabolism. Combined with Drosophila's robust genetic and immunofluorescence microscopy toolkits, studies of Drosophila fat body function are ripe for cell biological analysis. Unlike the larval fat body, which is easily
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Frictiotaxis underlies adhesion-independent durotaxis bioRxiv. Cell Biol. Pub Date : 2024-04-15 Adam Shellard, Kai W Weissenbruch, Peter Hampshire, Namid Stillman, Christina Dix, Richard Thorogate, Albane Imbert, Guillaume Charras, Ricard Alert, Roberto Mayor
Cells move directionally along gradients of substrate stiffness, a process called durotaxis. The current consensus is that durotaxis relies on cell substrate focal adhesions to sense stiffness and transmit forces that drive directed motion. Therefore, focal adhesion, independent durotaxis is thought to be impossible. Here, we show that confined cells can perform durotaxis despite lacking strong or
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Circadian desynchronization desensitizes insulin-producing cells to cytokine-mediated transcriptomic remodeling and cell death: a novel beta-cell anti-apoptotic response to inflammation bioRxiv. Cell Biol. Pub Date : 2024-04-15 Phillip Alexander Keller Andersen, Rasmus Henrik Reeh, Isabel Sanders, Emilie Bender Overlund, Thomas Mandrup-Poulsen
Perturbation of the circadian clock is a risk factor for metabolic diseases. Beta-Cell specific clock disruption causes glucose intolerance in mice, associated with oxidative stress and secretory failure in beta-cells. Proinflammatory cytokines alter the expression of core-clock machinery in human and rodent beta-cells, but the molecular mechanisms and consequences for cell viability are unclear. We
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Temporally controlled nervous system-to-gut signaling bidirectionally regulates longevity in Caenorhabditis elegans bioRxiv. Cell Biol. Pub Date : 2024-04-15 Lingxiu Xu, Chengxuan Han, Lei Chun, Shawn Xu, Jianfeng Liu
The nervous system modulates aging by secreting signaling molecules to cell-nonautonomously regulate the physiological state of distal tissues such as the gut. However, the underlying mechanisms are not well understood. Here, using Caenorhabditis elegans as a model, we identified two distinct neuroendocrine signaling circuits through which motor neurons signal the gut in early life to shorten lifespan
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Legumain is a paracrine regulator of osteoblast differentiation and mediates the inhibitory effect of TGF-β1 on osteoblast maturation bioRxiv. Cell Biol. Pub Date : 2024-04-15 Karl Martin Forbord, Ngoc Nguyen Lunde, Tatjana Bosnjak-Olsen, Harald Thidemann Johansen, Rigmor Solberg, Abbas Jafari
Transforming growth factor-beta 1 (TGF-β1) is a critical regulator of skeletal homeostasis and has diverse promoting effects on osteoblastogenesis. However, the mechanisms behind the intriguing inhibitory effect of TGF-β1 on osteoblast maturation are not fully understood. Here, we demonstrate a novel mechanism by which TGF-β1 modulates osteoblast maturation through lysosomal protease legumain. We observed
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psudo: Exploring Multi-Channel Biomedical Image Data with Spatially and Perceptually Optimized Pseudocoloring bioRxiv. Cell Biol. Pub Date : 2024-04-15 Simon Warchol, Jakob Troidl, Jeremy L Muhlich, Robert Krueger, John Hoffer, Tica Lin, Johanna Beyer, Elena Glassman, Peter Karl Sorger, Hanspeter Pfister
Over the past century, multichannel fluorescence imaging has been pivotal in myriad scientific breakthroughs by enabling the spatial visualization of proteins within a biological sample. With the shift to digital methods and visualization software, experts can now flexibly pseudocolor and combine image channels, each corresponding to a different protein, to explore their spatial relationships. We thus
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Proteomic profile analysis of plasma and aqueous humor from glaucoma and non-glaucomatous patients bioRxiv. Cell Biol. Pub Date : 2024-04-15 Carmen L Pessuti, Chia-Ling Huang, Angela Banks, Nhi Vo, Lori Jennings, Joseph Loureiro, Kleber Ribeiro, Deise Fialho Costa, Heloisa Nascimento, Cristina Muccioli, Ivan Maynart Tavares, Alessandra Commodaro, Rubens Belfort, Chrisopher Wilson, Amy Chen, Ganesh Prasanna, VijayKrishna Raghunathan
Purpose: Glaucoma, a multifactorial ocular neuropathic and age associated disease, can lead to irreversible vision loss. Diagnosis involves assessing optic cupping (increased cup-to-disc ratios) and structural changes (like retinal nerve fiber layer thinning) through clinical imaging. Elevated intraocular pressure (IOP) is commonly associated with glaucoma, but not always. However, understanding disease
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Poly (A) Binding Protein 2 is critical for stem-progenitor differentiation during regeneration in the planarian Schmidtea mediterranea. bioRxiv. Cell Biol. Pub Date : 2024-04-15 Namita Mukundan, Nivedita Hariharan, Vidyanand Sasidharan, Vairavan Lakshmanan, Dasaradhi Palakodeti, Colin Jamora
Post-transcriptional regulation has emerged as a key mechanism to regulate stem cell renewal and differentiation, which is essential for understanding tissue regeneration and homeostasis. Poly(A)-binding proteins are a family of RNA-binding proteins that play a vital role in post-transcriptional regulation by controlling mRNA stability and protein synthesis. The involvement of poly(A) binding proteins
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ScRNA-seq and scATAC-seq reveal that sertoli cell mediate spermatogenesis disorders through stage-specific communications in non-obstructive azoospermia bioRxiv. Cell Biol. Pub Date : 2024-04-14 Shimin Wang, Hongxian Wang, Bicheng Jin, Hongli Yan, Qingliang Zheng, Dong Zhao
Non-obstructive azoospermia (NOA) belongs to male infertility due to spermatogenesis failure. However, evidence for cell type-specific abnormalities of spermatogenesis disorders in NOA remains lacking. We performed single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on testicular tissues from patients with obstructive azoospermia(OA)
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p53 secures the normal behavior of H3.1 histone in the nucleus by regulating nuclear phosphatidic acid and EZH2 during the G1/S phase bioRxiv. Cell Biol. Pub Date : 2024-04-14 Tsukasa Oikawa, Junya Hasegawa, Haruka Handa, Naomi Ohnishi, Yasuhito Onodera, Ari Hashimoto, Junko Sasaki, Takehiko Sasaki, Koji Ueda, Hisataka Sabe
Histones are key molecules of epigenetic regulation and inheritance, and are thought to be chaperoned and transported into the nucleus appropriately prior to being integrated into nucleosomes. H3.1 histone is predominantly synthesized and enters the nucleus during the G1/S phase of the cell cycle, as a new component of duplicating nucleosomes. Here we found that p53 is necessary to secure the normal
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ARHGEF17/TEM4 regulates the cell cycle through control of G1 progression bioRxiv. Cell Biol. Pub Date : 2024-04-14 Sabine Elowe, Diogjena Katerina Prifti, Eva Calvo, Annie Lauzier, Chantal Garand, Romain Devillers, Suparba Roy, Alexsandro dos Santos, Laurence Descombes, Francois Bordeleau
The Ras homolog (Rho) small GTPases, via their role in regulating the actin cytoskeleton, coordinate diverse cellular functions including cell morphology, adhesion and motility, as well as cell cycle progression, survival and apoptosis. The upstream regulators for many of these functions are unknown. ARHGEF17 (also known as TEM4) is a Rho family guanine nucleotide exchange factor (GEF) that been implicated
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KIF2C-induced nuclear condensation concentrates PLK1 and phosphorylated BRCA2 at the kinetochore microtubules in mitosis bioRxiv. Cell Biol. Pub Date : 2024-04-14 Anastasiia Skobelkina, Manon Julien, Sylvain Jeannin, Simona Miron, Tom Egger, Rady Chaaban, Guillaume Bouvignies, Rania Ghouil, Claire Friel, Didier BUSSO, Francois-Xavier Theillet, Romain Le Bars, Aura Carreira, Angelos Constantinou, Jihane Basbous, SOPHIE ZINN-JUSTIN
During mitosis, the human microtubule depolymerase KIF2C increases the turnover of kinetochore-microtubule attachments. This facilitates the correction of attachment errors. Moreover, BRCA2 phosphorylated at Thr207 by PLK1 (BRCA2-pT207) assembles a complex including PLK1, PP2A and BUBR1 that contributes to the stability of the kinetochore-microtubule attachments. PLK1, together with Aurora B, critically
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The microtubule regulator EFA-6 forms spatially restricted cortical foci dependent on its intrinsically disordered region and interactions with tubulins bioRxiv. Cell Biol. Pub Date : 2024-04-14 Anjali Sandhu, Xiaohui Lyu, Xinghaoyun Wan, Xuefeng Meng, Ngang Heok Tang, Gilberto Gonzalez, Ishana N Syed, Lizhen Chen, Yishi Jin, Andrew D Chisholm
Microtubules (MTs) are dynamic components of the cytoskeleton and play essential roles in morphogenesis and maintenance of tissue and cell integrity. Despite recent advances in understanding of MT ultrastructure, organization, and growth control, how cells regulate MT organization at the cell cortex remains poorly understood. The EFA-6/EFA6 proteins are recently identified membrane associated proteins
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In-depth study of MPV17: a molecular travel unveiling a mitochondrial calcium regulation function bioRxiv. Cell Biol. Pub Date : 2024-04-14 Sebastien Meurant, Ilario Amato, Lorris Mauclet, Marc Dieu, Arnaud Chevrollier, Benjamin Ledoux, Marino Caruso, Guy Lenaers, Thierry Arnould, Patricia Renard
Mitochondrial DNA depletion syndromes are severe genetic disorders associated with mutations in a variety of genes including MPV17, encoding a protein of the inner mitochondrial membrane with an unclear function. In this study, using BioID technology, we identified MPV17 interacting partners among which proteins from the MICOS complex. However, MPV17 knockout did not impact mitochondrial ultrastructure
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TAM receptors control actomyosin dynamics in osteoclasts via RHOA-COFILIN-MYOSIN II signaling bioRxiv. Cell Biol. Pub Date : 2024-04-14 Janik Engelmann, Jennifer Zarrer, Max J Schmerder, Christian Mess, Deniz Ragipoglu, Kristoffer Riecken, Tal Burstyn-Cohen, Emily Alberto, Sourav Ghosh, Carla V Rothlin, Klaus Pantel, Carsten Bokemeyer, Eric Hesse, Hanna Taipaleenmaeki, Sonja Loges, Isabel Ben-Batalla
The TAM family of receptor tyrosine kinases were recently identified to regulate bone homeostasis by controlling osteoblasts and bone formation. Despite extensive knowledge of TAM receptor function in the mononuclear phagocyte system, the role of TAM receptors in osteoclasts remains largely unknown. Here, we identify a physiological regulatory system including MERTK and TYRO3 in osteoclasts controlling
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Lung megakaryocytes are long-lived, arise from Flt3-negative bone marrow cells, and contribute to platelet recovery in thrombocytopenia bioRxiv. Cell Biol. Pub Date : 2024-04-14 Alison Livada, Kathleen E McGrath, Michael Malloy, Chen Li, Sara K Ture, Paul D Kingsley, Anne D Koniski, Leah A Vit, Katherine E Nolan, Deanne Mickelsen, Grace Monette, Preeti Maurya, Jim Palis, Craig N Morrell
We previously characterized lung megakaryocytes (Mks) as largely extravascular cells with an immune modulatory phenotype (Pariser et al., 2021). Because bone marrow (BM) Mks are relatively short lived, it is assumed that extravascular lung Mks are constantly seeded from the BM, but there are no experimental data to validate this concept. To investigate lung Mk origin and how their origin may impact
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Huntingtin polyglutamine expansions misdirect axonal transport by perturbing motor and adaptor recruitment bioRxiv. Cell Biol. Pub Date : 2024-04-14 Emily N.P. Prowse, Brooke A. Turkalj, Muriel Sebastien, Daniel Beaudet, Heidi M. McBride, Gary J. Brouhard, Mahmoud A. Pouladi, Adam G Hendricks
Huntington's disease (HD) is caused by polyglutamine (polyQ) expansions in huntingtin (HTT). Polyglutamine repeat lengths >35Q lead to neurodegeneration and longer repeats correspond to earlier symptom onset. HTT scaffolds kinesin-1 and dynein to a variety of vesicles and organelles directly and through adaptors. To characterize the effects of HTT polyQ expansions on axonal transport, we tracked BDNF
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Crossover Interference Mediates Multiscale Patterning Along Meiotic Chromosomes bioRxiv. Cell Biol. Pub Date : 2024-04-14 Martin A White, Beth Weiner, Lingluo Chu, Gyubum Lim, Nancy E Kleckner
The classical phenomenon of crossover interference is a one-dimensional spatial patterning process that produces evenly spaced crossovers during meiosis. Quantitative analysis of diagnostic molecules along budding yeast chromosomes reveals that this process also sets up a second, interdigitated pattern of related but longer periodicity, in a "two-tiered" patterning process. The second tier corresponds
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Soluble αβ-tubulins reversibly sequester TTC5 to regulate tubulin mRNA decay bioRxiv. Cell Biol. Pub Date : 2024-04-13 Alina Batiuk, Markus Höpfler, Ana C. Almeida, Deryn T. En-Jie, Oscar Vadas, Evangelia Vartholomaiou, Ramanujan S Hegde, Zhewang Lin, Ivana Gasic
Microtubules, built from heterodimers of α- and β-tubulins, control cell shape, mediate intracellular transport and power cell division. The concentration of αβ-tubulins is tightly controlled through a post-transcriptional mechanism involving selective and regulated degradation of tubulin-encoding mRNAs. Degradation is initiated by TTC5, which recognizes tubulin-synthesizing ribosomes and recruits
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Triglyceride metabolism controls inflammation and APOE4-associated disease states in microglia bioRxiv. Cell Biol. Pub Date : 2024-04-13 Roxan A Stephenson, Kory R Johnson, Linling Cheng, Linda G Yang, Jessica T Root, Jaanam Gopalakrishnan, Han-Yu Shih, Priyanka S Narayan
Microglia modulate their cell state in response to various stimuli. Changes to cellular lipids often accompany shifts in microglial cell state, but the functional significance of these metabolic changes remains poorly understood. In human induced pluripotent stem cell-derived microglia, we observed that both extrinsic activation (by lipopolysaccharide treatment) and intrinsic triggers (the Alzheimers
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Glutamylation imbalance leads to photoreceptor degeneration bioRxiv. Cell Biol. Pub Date : 2024-04-13 Olivier Mercey, Sudarshan Gadadhar, Maria Magdalena Magiera, Laura Lebrun, Corinne Kostic, Alexandre Moulin, Yvan Arsenijevic, Carsten Janke, Paul Guichard, Virginie Hamel
The stereotypic structure of microtubules, assembled from conserved alpha/beta-tubulin dimers is subject to a complex diversity of Post-translational Modifications (PTMs). PTMs are predicted to fine-tune microtubule properties and interactions with other proteins, thus allowing microtubules to perform specific functions. Cilia accumulate several types of tubulin PTMs, such as polyglutamylation, polyglycylation
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The G-Protein Couple Receptor Kinase 2 (GRK2) Orchestrates Hair Follicle Homeostasis bioRxiv. Cell Biol. Pub Date : 2024-04-12 Alejandro Asensio, Maria Sanz-Flores, Kif Liakath-Ali, Julia Palacios, Jesus M Paramio, Ramon Garcia-Escudero, Federico Mayor, Catalina Ribas
Tightly regulated cell-cell and cell-niche intercommunications via complex signaling networks are involved in maintaining normal hair follicle (HF) homeostasis, cycling and cell fate determination. However, knowledge of specific mechanisms by which hair loss takes place under pathological situations is still needed. Using a keratinocyte-specific knockout mouse model, we uncover that the G protein-coupled
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Resistance to Naive and Formative Pluripotency Conversion in RSeT Human Embryonic Stem Cells bioRxiv. Cell Biol. Pub Date : 2024-04-12 Kevin G Chen, Kory J Johnson, Kyeyoon Park, Dragan Maric, Forest Yang, Wen Fang Liu, Yang C Fann, Barbara S Mallon, Pamela G Robey
One of the most important properties of human embryonic stem cells (hESCs) is related to their primed and naive pluripotent states. Our previous meta-analysis indicates the existence of heterogeneous pluripotent states derived from diverse naive protocols. In this study, we have characterized a commercial medium (RSeT)-based pluripotent state under various growth conditions. Notably, RSeT hESCs can
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Mechanical stress through growth on stiffer substrates impacts animal health and longevity in C. elegans. bioRxiv. Cell Biol. Pub Date : 2024-04-12 Maria Oorloff, Adam Hruby, Maxim Averbukh, Athena Alcala, Naibedya Dutta, Toni Castro Torres, Darius Moaddeli, Matthew Vega, Juri Kim, Andrew Bong, Aeowynn J Coakley, Daniel Hicks, Jing Wang, Tiffany Wang, Sally Hoang, Kevin M Tharp, Gilberto Garcia, Ryo Sanabria
Mechanical stress is a measure of internal resistance exhibited by a body or material when external forces, such as compression, tension, bending, etc. are applied. The study of mechanical stress on health and aging is a continuously growing field, as major changes to the extracellular matrix and cell-to-cell adhesions can result in dramatic changes to tissue stiffness during aging and diseased conditions
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The G1/S transition is promoted by Rb degradation via the E3 ligase UBR5 bioRxiv. Cell Biol. Pub Date : 2024-04-12 Shuyuan Zhang, Lucas Fuentes Valenzuela, Evgeny Zatulovskiy, Lise Fiona Sarah Mangiante, Christina Curtis, Jan Skotheim
Mammalian cells make the decision to divide at the G1/S transition in response to diverse signals impinging on the retinoblastoma protein Rb, a cell cycle inhibitor and tumor suppressor. Rb is inhibited by two parallel pathways. In the canonical pathway, Cyclin D-Cdk4/6 kinase complexes phosphorylate and inactivate Rb. In the second, recently discovered pathway, Rb concentration decreases during G1
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Multiplexed in vivo imaging with fluorescence lifetime modulating tags bioRxiv. Cell Biol. Pub Date : 2024-04-12 Lina El Hajji, France Lam, Maria Avtodeeva, Hela Benaissa, Christine Rampon, Michel Volovitch, Sophie Vriz, Arnaud Gautier
Fluorescence lifetime imaging opens new dimensions for highly multiplexed imaging in live cells and organisms using differences in fluorescence lifetime to distinguish spectrally identical fluorescent probes. Here, we describe a set of fluorescence-activating and absorption-shifting tags (FASTs) capable of modulating the fluorescence lifetime of embedded fluorogenic 4-hydroxybenzylidene rhodanine (HBR)
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The neuroendocrine transition in prostate cancer is dynamic and dependent on ASCL1 bioRxiv. Cell Biol. Pub Date : 2024-04-11 Rodrigo Romero, Tinyi Chu, Tania J. González-Robles, Perianne Smith, Yubin Xie, Harmanpreet Kaur, Sara Yoder, Huiyong Zhao, Chenyi Mao, Wenfei Kang, Maria V. Pulina, Kayla E. Lawrence, Anuradha Gopalan, Samir Zaidi, Kwangmin Yoo, Jungmin Choi, Ning Fan, Olivia Gerstner, Wouter R. Karthaus, Elisa DeStanchina, Kelly V. Ruggles, Peter M.K. Westcott, Ronan Chaligné, Dana Pe’er, Charles L. Sawyers
Lineage plasticity is a recognized hallmark of cancer progression that can shape therapy outcomes. The underlying cellular and molecular mechanisms mediating lineage plasticity remain poorly understood. Here, we describe a versatile in vivo platform to identify and interrogate the molecular determinants of neuroendocrine lineage transformation at different stages of prostate cancer progression. Adenocarcinomas
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The uptake of small extracellular vesicles by recipient cells is facilitated by paracrine adhesion signaling bioRxiv. Cell Biol. Pub Date : 2024-04-11 Koichiro M. Hirosawa, Yusuke Sato, Rinshi S. Kasai, Eriko Yamaguchi, Naoko Komura, Hiromune Ando, Ayuko Hoshino, Yasunari Yokota, Kenichi G. N. Suzuki
Small extracellular vesicles (sEVs) play critical roles in intercellular communication. However, the mechanisms by which sEVs are internalized by recipient cells remain unclear. Here, we investigated these mechanisms through state-of-the-art imaging techniques. Single-molecule imaging revealed that tumor-derived sEVs can be divided into several subtypes. By simultaneously performing single sEV-particle
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Extracellular vesicles adhere to cells predominantly through the interaction of CD151-associated integrin heterodimers and GM1 with laminin bioRxiv. Cell Biol. Pub Date : 2024-04-11 Tatsuki Isogai, Koichiro M. Hirosawa, Miki Kanno, Ayano Sho, Rinshi S. Kasai, Naoko Komura, Hiromune Ando, Keiko Furukawa, Yuhsuke Ohmi, Koichi Furukawa, Yasunari Yokota, Kenichi G. N. Suzuki
Summary Quantitative assessments using single-molecule imaging and super-resolution microscopy revealed that all extracellular vesicle subtypes derived from four distinct tumor cell lines, regardless of size, bind to laminin predominantly via CD151-facilitated integrin heterodimers and GM1, but not as much to fibronectin.
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The G1/S transition in mammalian stem cells in vivo is autonomously regulated by cell size bioRxiv. Cell Biol. Pub Date : 2024-04-11 Shicong Xie, Shuyuan Zhang, Gustavo de Medeiros, Prisca Liberali, Jan M. Skotheim
Cell growth and division must be coordinated to maintain a stable cell size, but how this coordination is implemented in multicellular tissues remains unclear. In unicellular eukaryotes, autonomous cell size control mechanisms couple cell growth and division with little extracellular input. However, in multicellular tissues we do not know if autonomous cell size control mechanisms operate the same
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Targeting phosphatase DUSP22 ameliorates skeletal muscle wasting via Akt independent JNK-FOXO3a repression bioRxiv. Cell Biol. Pub Date : 2024-04-11 Sang-Hoon Lee, Hyun-Jun Kim, Seon-Wook Kim, Hyunju Lee, Da-Woon Jung, Darren Reece Williams
Skeletal muscle wasting results from numerous conditions, such as sarcopenia, glucocorticoid therapy or intensive care. It prevents independent living in the elderly, predisposes to secondary diseases, and ultimately reduces lifespan. There is no approved drug therapy and the major causative mechanisms are not fully understood. Dual specificity phosphatase 22 (DUSP22) is a pleiotropic signaling molecule
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Humanized in vivo bone marrow models orchestrate multi-lineage human hematopoietic cell development bioRxiv. Cell Biol. Pub Date : 2024-04-11 Laurent Renou, Wenjie Sun, Chloe Friedrich, Klaudia Galant, Cecile Conrad, Evelia Plantier, Katharina Schallmoser, Linda Krisch, Vilma Barroca, Saryami Devanand, Nathalie Déchamp, Andreas Reinisch, Jelena Martinovic, Alessandra Magnani, Lionel Faivre, Julien Calvo, Leila Perie, Olivier Kosmider, Françoise Pflumio
Hematopoiesis develops in the bone marrow (BM) where multiple interactions regulate differentiation and preservation of hematopoietic stem/progenitor cells (HSPCs). Although murine BM has been extensively analyzed, the human BM microenvironment remains less understood. Immune-deficient murine models have enabled the analysis of molecular and cellular regulation of human HSPCs, which remains limited
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Mechanical confinement induces ferroptosis through mitochondrial dysfunction bioRxiv. Cell Biol. Pub Date : 2024-04-11 Fang Zhou, Robert J. Ju, Chenlu Kang, Jiayi Li, Ao Yang, Alexandre Libert, Yujie Sun, Ling Liang, Xiaoqing Hu, Samantha J. Stehbens, Congying Wu
Cells exist in highly crowded environments where they are exposed to fluctuating mechanical forces arising from surrounding cells and the extracellular matrix microenvironment. In these settings, external forces are transmitted to intracellular organelles including the nucleus. While cells can survive confinement, extended duration of confinement or confinement in settings where cells are unable to
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Inactivation of a non-canonical gp130 signaling arm attenuates chronic systemic inflammation and multimorbidity induced by a high-fat diet bioRxiv. Cell Biol. Pub Date : 2024-04-11 Youngjoo Lee, Arijita Sarkar, Jade Tassey, Jonathan N. Levi, Siyoung Lee, Nancy Q. Liu, Andrew C. Drake, Jenny Magallanes, Una Stevic, Jinxiu Lu, Dawei Ge, Hanhan Tang, Tadiwanashe Mkaratigwa, Fangzhou Bian, Ruzanna Shkhyan, Michael Bonaguidi, Denis Evseenko
Interleukin-6 (IL-6) is a major pro-inflammatory cytokine for which the levels in plasma demonstrate a robust correlation with age and body mass index (BMI) as part of the senescence-associated secretory phenotype. IL-6 cytokines also play a crucial role in metabolic homeostasis and regenerative processes, primarily via the canonical STAT3 pathway. Thus, selective modulation of IL-6 signaling may offer
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A combination of major histocompatibility complex (MHC) I overexpression and type I interferon induce mitochondrial dysfunction in human skeletal myoblasts bioRxiv. Cell Biol. Pub Date : 2024-04-11 Anastasia Thoma, Holly L Bond, Tania Akter-Miah, Nasser Al-Shanti, Hans Degens, Vanja Pekovic-Vaughan, Adam P Lightfoot
The overexpression of major histocompatibility complex (MHC) I on the surface of muscle fibres is a characteristic hallmark of the idiopathic inflammatory myopathies (IIMs), collectively termed myositis. Alongside MHC-I overexpression, sub-types of myositis, display a distinct type I interferon (IFN) signature. This study examined the combinational effects of elevated MHC-I and type I IFNs (IFNα/β)
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Photochromic reversion enables long-term tracking of single molecules in living plants. bioRxiv. Cell Biol. Pub Date : 2024-04-12 Michelle von Arx, Kaltra Xhelilaj, Philip Schulz, Sven zur Oven-Krockhaus, Julien Gronnier
Single-molecule imaging promises the observation of individual molecules at work in living cells. In plants, however, the tracking of single molecules is generally limited to mere hundred milliseconds, making it virtually impossible to observe live dynamic cellular events with molecular resolution. Here, we introduce photochromic reversion which uses the reversion of EOS fluorescent protein's dark
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Myogenic Anti-Nucleolin Aptamer iSN04 Inhibits Proliferation and Promotes Differentiation of Vascular Smooth Muscle Cells bioRxiv. Cell Biol. Pub Date : 2024-04-11 Mana Miyoshi, Takeshi Shimosato, Tomohide Takaya
De-differentiation and subsequent increased proliferation and inflammation of vascular smooth muscle cells (VSMCs) is one of the mechanisms of atherogenesis. Maintaining VSMCs in a contractile differentiated state is therefore a promising therapeutic strategy for atherosclerosis. We have reported the 18-base myogenetic oligodeoxynucleotide, iSN04, which serves as an anti-nucleolin aptamer and promotes
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Quantitative intra-Golgi transport and organization data suggest the stable compartment nature of the Golgi bioRxiv. Cell Biol. Pub Date : 2024-04-11 Hieng Chiong Tie, Haiyun Wang, Divyanshu Mahajan, Xiuping Sun, Bing Chen, Lei Lu
How the intra-Golgi secretory transport works remains a mystery. The cisternal progression and the stable compartment models have been proposed and are under debate. Classic cisternal progression model posits that both the intra-Golgi transport and Golgi exit of secretory cargos should occur at a constant velocity dictated by the cisternal progression; furthermore, COPI-mediated intra-Golgi retrograde
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Lgr5+ intestinal stem cells are required for organoid survival after genotoxic injury bioRxiv. Cell Biol. Pub Date : 2024-04-11 Joseph Lee, Antoine Gleizes, Felipe Takaesu, Sarah F Webster, Taylor Hailstock, Adam D Gracz
Progenitors and mature cells can maintain the intestinal epithelium by dedifferentiation and facultative intestinal stem cell (fISC) function when active ISCs (aISCs) are lost to damage. Here, we sought to model fISC activation in intestinal organoids with doxorubicin (DXR), a chemotherapeutic known to ablate Lgr5+ aISCs in vivo. We identified low and high doses of DXR compatible with long-term organoid
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Efficient Generation of Human Pluripotent Stem Cells from Frozen Cord Tissue via Chemical Reprogramming bioRxiv. Cell Biol. Pub Date : 2024-04-11 Coneria Nansubuga, Donna K. Mahnke, Siqi Li, Abigail Multerer, Jake Minx, Bradley Miller, Mengcheng Shen, Andreas Beyer, Lu Han, Joy Lincoln, Chun Liu
Chemical reprogramming presents an innovative approach for generating induced pluripotent stem cells (iPSCs), bypassing the genetic instability and safe concern associated with viral vector approach. We describe a novel, efficient chemical method for reprogramming human umbilical cord tissue-derived mesenchymal stem cells (MSCs) into induced pluripotent stem cells (iPSCs). Compared to previous sources