Emergency myelopoiesis (EM) is essential in immune defense against pathogens for rapid replenishing of mature myeloid cells. During the EM process, a rapid cell-cycle switch from the quiescent hematopoietic stem cells (HSCs) to highly proliferative myeloid progenitors (MPs) is critical. How the rapid proliferation of MPs during EM is regulated remains poorly understood. Here, we reveal that ATG7, a critical autophagy factor, is essential for the rapid proliferation of MPs during human myelopoiesis. Peripheral blood (PB)-mobilized hematopoietic stem/progenitor cells (HSPCs) with knockdown or HSPCs derived from human embryonic stem cells (hESCs) exhibit severe defect in proliferation during fate transition from HSPCs to MPs. Mechanistically, we show that ATG7 deficiency reduces p53 localization in lysosome for a potential autophagy-mediated degradation. Together, we reveal a previously unrecognized role of autophagy to regulate p53 for a rapid proliferation of MPs in human myelopoiesis.

中文翻译：

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自噬对于人类骨髓细胞生成至关重要

紧急骨髓生成（EM）对于针对病原体的免疫防御以及快速补充成熟骨髓细胞至关重要。在 EM 过程中，从静止造血干细胞 (HSC) 到高度增殖的骨髓祖细胞 (MP) 的快速细胞周期转换至关重要。 EM 期间 MP 的快速增殖是如何受到调节的仍然知之甚少。在此，我们揭示了 ATG7 作为一种关键的自噬因子，对于人类骨髓细胞生成过程中 MP 的快速增殖至关重要。敲低的外周血 (PB) 动员的造血干/祖细胞 (HSPC) 或源自人胚胎干细胞 (hESC) 的 HSPC 在从 HSPC 到 MP 的命运转变过程中表现出严重的增殖缺陷。从机制上讲，我们发现 ATG7 缺陷会减少 p53 在溶酶体中的定位，从而导致潜在的自噬介导的降解。我们共同揭示了自噬在调节 p53 促进人类骨髓细胞生成中 MP 快速增殖方面的先前未被认识的作用。