Differential cytokine contributions of perivascular haematopoietic stem cell niches.
Differential cytokine contributions of perivascular haematopoietic stem cell niches.
复制标题
DOI：
10.1038/ncb3475
复制
发表时间：
2017-03
影响因子：
21.3
通讯作者：
Frenette PS
中科院分区：
文献类型：
--
作者：
Asada N;Kunisaki Y;Pierce H;Wang Z;Fernandez NF;Birbrair A;Ma'ayan A;Frenette PS
骨髓的小动脉和血窦伴随着表达神经/神经胶质抗原2(NG2)和瘦素受体(Lepr)的基质细胞，并构成调节造血干细胞(HSCs)静止和增殖的特殊利基。然而，利基细胞如何差异化地调节HSC的功能仍不清楚。在这里，我们表明，细胞因子调节HSC功能的效果依赖于产生细胞的来源。从所有Nestin-GFP标记的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 HSCs。小动脉NG2+细胞中CXCL12的选择性缺失，而不是肝窦Lepr+细胞中CXCL12的选择性缺失，导致HSC减少并改变了BM中HSC的定位。相比之下，Lepr+细胞中SCF的缺失，而不是NG2+细胞中的SCF缺失，导致了BM HSC数量的减少。这些结果揭示了来自不同血管壁龛中的血管周围细胞的细胞因子对HSC维持的不同贡献。
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 specialised 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 localisation 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.