Cell morphology heterogeneity within epithelial collectives is a pervasive phenomenon intertwined with tissue mechanical properties. Despite its widespread occurrence, the underlying mechanisms driving cell morphology heterogeneity and its consequential biological ramifications remain elusive. Here, we investigate the dynamic evolution of epithelial cell morphology and nucleus morphology during crowding, unveiling a consistent correlation between the two. Our investigation reveals a persistent log-normal probability distribution characterizing both cell and nucleus areas across diverse crowding stages and epithelial model systems. We showed that this morphological diversity arises from asymmetric partitioning during cell division and is perpetuated through actomyosin-mediated regulation of cell-nucleus size coordination. Moreover, we provide insights into the impact of nucleus morphology on chromatin dynamics, demonstrating that constraining nucleus area leads to downregulation of the euchromatic mark H3K9ac and upregulation of the heterochromatic mark H3K27me3 through modulation of histone demethylase UTX expression. These findings underscore the significance of cell morphology heterogeneity as a driver of chromatin state diversity, shaping functional variability within epithelial tissues.

中文翻译：

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通过协调细胞核大小和上皮细胞形态异质性调节染色质修饰

上皮细胞集体内的细胞形态异质性是一种与组织机械性能交织在一起的普遍现象。尽管其广泛存在，但驱动细胞形态异质性及其随之而来的生物学后果的潜在机制仍然难以捉摸。在这里，我们研究了拥挤过程中上皮细胞形态和细胞核形态的动态演化，揭示了两者之间的一致相关性。我们的研究揭示了不同拥挤阶段和上皮模型系统中细胞和细胞核区域特征的持续对数正态概率分布。我们表明，这种形态多样性源于细胞分裂过程中的不对称分配，并通过肌动球蛋白介导的细胞核大小协调调节而得以延续。此外，我们还深入了解了细胞核形态对染色质动力学的影响，证明限制细胞核面积可通过调节组蛋白去甲基化酶 UTX 表达，导致常染色质标记 H3K9ac 下调和异染色质标记 H3K27me3 上调。这些发现强调了细胞形态异质性作为染色质状态多样性驱动因素的重要性，塑造上皮组织内的功能变异性。