Bmi1 restricts the adipogenic differentiation of bone marrow stromal cells to maintain the integrity of the hematopoietic stem cell niche
Bmi1 restricts the adipogenic differentiation of bone marrow stromal cells to maintain the integrity of the hematopoietic stem cell niche
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DOI：
10.1016/j.exphem.2019.07.006
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发表时间：
2019-08-01
影响因子：
2.6
通讯作者：
Iwama, Atsushi
中科院分区：
文献类型：
--
作者：
Kato, Yuko;Hou, Li-Bo;Iwama, Atsushi
Polycomb组蛋白BMI1保持造血干细胞（HSC）功能。我们先前报道说，缺乏BMIL的小鼠在骨髓（BM）中表现出进行性脂肪变化。 HSC的很大一部分位于血管周围的细胞中，部分由内皮细胞和瘦素受体（+）（LEPR（+））BM基质细胞产生。为了阐明BMI1如何调节HSC利基市场，我们在小鼠的LEPR（+）细胞中专门删除了BMI1。 BMIL缺失促进了LEPR（+）基质细胞的脂肪生成分化，并随着年龄的增长而导致肢体骨骼的BM的进行性脂肪变化，从而导致BM中HSC和祖细胞数量减少并增强了硫外造血性血肿。辐照后BM再生期间，这种掺杂变化也很明显。几种掺杂调节基因似乎受BMI1的调节。我们的结果表明，BMI1保持在BM基质细胞中抑制的脂肪生成分化程序，以维持HSC生态位的完整性。 （c）2019 ISEH-血液学和干细胞学会。由Elsevier Inc.发布的所有权利保留。
The polycomb group protein Bmi1 maintains hematopoietic stem cell (HSC) functions. We previously reported that Bmil-deficient mice exhibited progressive fatty changes in bone marrow (BM). A large portion of HSCs reside in the perivascular niche created partly by endothelial cells and leptin receptor(+) (LepR(+)) BM stromal cells. To clarify how Bmi1 regulates the HSC niche, we specifically deleted Bmi1 in LepR(+) cells in mice. The Bmil deletion promoted the adipogenic differentiation of LepR(+) stromal cells and caused progressive fatty changes in the BM of limb bones with age, resulting in reductions in the numbers of HSCs and progenitors in BM and enhanced extramedullary hematopoiesis. This adipogenic change was also evident during BM regeneration after irradiation. Several adipogenic regulator genes appeared to be regulated by Bmi1. Our results indicate that Bmi1 keeps the adipogenic differentiation program repressed in BM stromal cells to maintain the integrity of the HSC niche. (C) 2019 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.