FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cells
FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cells
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DOI：
10.1182/blood-2010-06-288589
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发表时间：
2010-12-02
期刊：
影响因子：
20.3
通讯作者：
Guan, Jun-Lin
中科院分区：
文献类型：
--
作者：
Liu, Fei;Lee, Jae Y.;Guan, Jun-Lin
关于自噬机制在造血干细胞（HSC）中是否活跃以及它们是如何被调节的知之甚少。FIP 200（200-kDa FAK家族相互作用蛋白）在哺乳动物自噬和其他细胞功能中起重要作用，但其在造血细胞中的作用尚未被研究。在这里，我们表明造血细胞中FIP 200的条件性缺失导致围产期死亡和严重贫血。FIP 200是细胞自主需要的胎儿造血干细胞的维持和功能。FIP 200缺陷型HSC不能重建致死辐射受体。FIP 200消融并未导致HSC凋亡增加，但其确实增加了HSC增殖速率。与FIP 200在自噬中的重要作用一致，FIP 200缺失的胎儿HSC表现出线粒体质量和活性氧增加。这些数据将FIP 200鉴定为胎儿HSC的关键内在调节因子，并暗示自噬在维持胎儿造血和HSC中的潜在作用。（血。2010;116（23）：4806-4814）
Little is known about whether autophagic mechanisms are active in hematopoietic stem cells (HSCs) or how they are regulated. FIP200 (200-kDa FAK-family interacting protein) plays important roles in mammalian autophagy and other cellular functions, but its role in hematopoietic cells has not been examined. Here we show that conditional deletion of FIP200 in hematopoietic cells leads to perinatal lethality and severe anemia. FIP200 was cell-autonomously required for the maintenance and function of fetal HSCs. FIP200-deficient HSC were unable to reconstitute lethally irradiated recipients. FIP200 ablation did not result in increased HSC apoptosis, but it did increase the rate of HSC proliferation. Consistent with an essential role for FIP200 in autophagy, FIP200-null fetal HSCs exhibited both increased mitochondrial mass and reactive oxygen species. These data identify FIP200 as a key intrinsic regulator of fetal HSCs and implicate a potential role for autophagy in the maintenance of fetal hematopoiesis and HSCs. (Blood. 2010;116(23):4806-4814)