骨髓
造血
间质细胞
干细胞
祖细胞
生物
细胞生物学
再生(生物学)
造血干细胞
平衡
癌症研究
免疫学
作者
Meng Zhao,Tao Fang,Aparna Venkatraman,Zhenrui Li,Sarah E. Smith,Jay R. Unruh,Shiyuan Chen,Chris Ward,Pengxu Qian,John M. Perry,Heather Marshall,Jinxi Wang,Xi He,Linheng Li
出处
期刊:Cell Reports
[Elsevier]
日期:2019-01-01
卷期号:26 (3): 652-669.e6
被引量:123
标识
DOI:10.1016/j.celrep.2018.12.093
摘要
Regulation of hematopoietic stem cells (HSCs) by bone marrow (BM) niches has been extensively studied; however, whether and how HSC subpopulations are distinctively regulated by BM niches remain unclear. Here, we functionally distinguished reserve HSCs (rHSCs) from primed HSCs (pHSCs) based on their response to chemotherapy and examined how they are dichotomously regulated by BM niches. Both pHSCs and rHSCs supported long-term hematopoiesis in homeostasis; however, pHSCs were sensitive but rHSCs were resistant to chemotherapy. Surviving rHSCs restored the HSC pool and supported hematopoietic regeneration after chemotherapy. The rHSCs were preferentially maintained in the endosteal region that enriches N-cadherin+ (N-cad+) bone-lining cells in homeostasis and post-chemotherapy. N-cad+ cells were functional bone and marrow stromal progenitor cells (BMSPCs), giving rise to osteoblasts, adipocytes, and chondrocytes in vitro and in vivo. Finally, ablation of N-cad+ niche cells or deletion of SCF from N-cad+ niche cells impaired rHSC maintenance during homeostasis and regeneration.
科研通智能强力驱动
Strongly Powered by AbleSci AI