Asada Noboru, Kunisaki Yuya, Pierce Halley, Wang Zichen, Fernandez Nicolas F, Birbrair Alexander, Ma'ayan Avi, Frenette Paul S
Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Nat Cell Biol. 2017 Mar;19(3):214-223. doi: 10.1038/ncb3475. Epub 2017 Feb 20.
Arterioles and sinusoids of the bone marrow (BM) are accompanied by stromal cells that express nerve/glial antigen 2 (NG2) and leptin receptor (LepR), and constitute specialized niches that regulate quiescence and proliferation of haematopoietic stem cells (HSCs). However, how niche cells differentially regulate HSC functions remains unknown. Here, we show that the effects of cytokines regulating HSC functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand 12 (Cxcl12) or stem cell factor (Scf) from all perivascular cells marked by nestin-GFP dramatically depleted BM HSCs. Selective Cxcl12 deletion from arteriolar NG2 cells, but not from sinusoidal LepR cells, caused HSC reductions and altered HSC localization in BM. By contrast, deletion of Scf in LepR cells, but not NG2 cells, led to reductions in BM HSC numbers. These results uncover distinct contributions of cytokines derived from perivascular cells in separate vascular niches to HSC maintenance.
骨髓（BM）的小动脉和血窦伴随着表达神经/胶质抗原2（NG2）和瘦素受体（LepR）的基质细胞，这些基质细胞构成了调节造血干细胞（HSC）静止和增殖的特殊微环境。然而，微环境细胞如何差异调节HSC功能仍不清楚。在这里，我们表明调节HSC功能的细胞因子的作用取决于产生细胞的来源。从由巢蛋白绿色荧光蛋白（nestin-GFP）标记的所有血管周围细胞中删除趋化因子C-X-C基序配体12（Cxcl12）或干细胞因子（Scf），会显著耗尽BM HSC。从小动脉NG2细胞而非血窦LepR细胞中选择性删除Cxcl12，会导致HSC减少并改变HSC在BM中的定位。相比之下, 在LepR细胞而非NG2细胞中删除Scf，会导致BM HSC数量减少。这些结果揭示了来自不同血管微环境中血管周围细胞的细胞因子对HSC维持的不同贡献。
