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Nature:造血干细胞细胞龛内不同细胞类型的空间分布

录入:liuxiaod…    文章来源:生物谷    点击数:    更新时间:2013-11-1

  Paul Frenette 及同事采用“全标本共焦免疫荧光成像和计算模拟”方法对造血干细胞(HSC)细胞龛内不同细胞类型的空间分布进行了研究。

  他们发现,静止的HSC专门与优先在“骨内骨髓”中发现的小动脉关联,这些小动脉是保持HSC静止所必需的。

  因此这些结果表明,不同的HSC细胞龛(静止的或增殖性的)是由不同血管类型所赋予的。

  Nature doi:10.1038/nature12612

  Arteriolar niches maintain haematopoietic stem cell quiescence

  Yuya Kunisaki,Ingmar Bruns,Christoph Scheiermann,Jalal Ahmed,Sandra Pinho,Dachuan Zhang,Toshihide Mizoguchi,Qiaozhi Wei,Daniel Lucas,Keisuke Ito,Jessica C. Mar,Aviv Bergman & Paul S. Frenette

  Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant three-dimensional associations in the mouse bone marrow among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal bone marrow. These arterioles are ensheathed exclusively by rare NG2 (also known as CSPG4)+ pericytes, distinct from sinusoid-associated leptin receptor (LEPR)+ cells. Pharmacological or genetic activation of the HSC cell cycle alters the distribution of HSCs from NG2+ periarteriolar niches to LEPR+ perisinusoidal niches. Conditional depletion of NG2+ cells induces HSC cycling and reduces functional long-term repopulating HSCs in the bone marrow. These results thus indicate that arteriolar niches are indispensable for maintaining HSC quiescence.





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