PDF(Pubmed)
Abstract：
Hematopoietic stem cells (HSCs) produce all essential cellular components of the blood. Stromal cell lines supporting HSCs follow a vascular smooth muscle cell (vSMC) differentiation pathway, suggesting that some hematopoiesis-supporting cells originate from vSMC precursors. These pericyte-like precursors were recently identified in the aorta-gonad-mesonephros (AGM) region; however, their role in the hematopoietic development in vivo remains unknown. Here, we identify a subpopulation of NG2+Runx1+ perivascular cells that display a sclerotome-derived vSMC transcriptomic profile. We show that deleting Runx1 in NG2+ cells impairs the hematopoietic development in vivo and causes transcriptional changes in pericytes/vSMCs, endothelial cells and hematopoietic cells in the murine AGM. Importantly, this deletion leads also to a significant reduction of HSC reconstitution potential in the bone marrow in vivo. This defect is developmental, as NG2+Runx1+ cells were not detected in the adult bone marrow, demonstrating the existence of a specialised pericyte population in the HSC-generating niche, unique to the embryo.
摘要：
造血干细胞(HSC)产生血液的所有必需细胞成分。支持HSC的基质细胞系遵循血管平滑肌细胞（vSMC）分化途径，这表明一些造血支持细胞源自vSMC前体。最近在主动脉-性腺-中肾（AGM）区域发现了这些周细胞样前体；然而，它们在体内造血发育中的作用仍然未知。这里,我们确定了NG2+Runx1+血管周细胞亚群,其显示了一个来自巩膜组的vSMC转录组特征.我们表明，在NG2+细胞中删除Runx1会损害体内造血发育，并导致周细胞/vSMC的转录变化，鼠AGM中的内皮细胞和造血细胞。重要的是,这种缺失还导致体内骨髓中HSC重建潜力的显著降低。这个缺陷是发育性的,因为在成人骨髓中未检测到NG2+Runx1+细胞，证明了在产生HSC的利基中存在专门的周细胞种群，独特的胚胎。
