Autophagy is dispensable for the maintenance of hematopoietic stem cells in neonates
Autophagy is dispensable for the maintenance of hematopoietic stem cells in neonates
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DOI：
10.1182/bloodadvances.2020002410
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发表时间：
2021-03-13
期刊：
影响因子：
7.5
通讯作者：
Suda, Toshio
中科院分区：
文献类型：
--
作者：
Hashimoto, Michihiro;Umemoto, Terumasa;Suda, Toshio
造血干细胞（HSCs）进行自我更新或分化以维持终身造血。造血干细胞处于低线粒体活性的静止状态。近期研究表明，自噬通过抑制线粒体代谢促进造血干细胞的静止。然而，自噬是否参与活跃增殖的新生儿造血干细胞的调控仍不清楚。在本研究中，我们利用两种自噬相关基因7（Atg7）条件性敲除小鼠：Mx1 - Cre诱导系统和Vav - Cre系统，阐明了自噬在新生儿造血干细胞中的作用。Atg7缺陷的造血干细胞表现出过度的细胞分裂以及线粒体代谢增强，导致成年期骨髓衰竭。然而，Atg7缺陷对新生儿阶段造血干细胞的造血功能和代谢状态影响极小。此外，Atg7缺陷的新生儿造血干细胞表现出长期重建活性，与野生型新生儿造血干细胞相当。综上所述，自噬对于新生儿的干细胞功能和造血稳态是可有可无的，这为自噬在造血干细胞调控中的作用提供了一个新的视角。
Hematopoietic stem cells (HSCs) undergo self-renewal or differentiation to sustain lifelong hematopoiesis. HSCs are preserved in quiescence with low mitochondrial activity. Recent studies indicate that autophagy contributes to HSC quiescence through suppressing mitochondrial metabolism. However, it remains unclear whether autophagy is involved in the regulation of neonatal HSCs, which proliferate actively. In this study, we clarified the role of autophagy in neonatal HSCs using 2 types of autophagy-related gene 7 (Atg7)-conditional knockout mice: Mx1-Cre inducible system and Vav-Cre system. Atg7-deficient HSCs exhibited excess cell divisions with enhanced mitochondrial metabolism, leading to bone marrow failure at adult stage. However, Atg7 deficiency minimally affected hematopoiesis and metabolic state in HSCs at neonatal stage. In addition, Atg7-deficient neonatal HSCs exhibited long-term reconstructing activity, equivalent to wild-type neonatal HSCs. Taken together, autophagy is dispensable for stem cell function and hematopoietic homeostasis in neonates and provide a novel aspect into the role of autophagy in the HSC regulation.