Majeti Ravindra, Park Christopher Y, Weissman Irving L
Department of Internal Medicine, Division of Hematology, Stanford University, Palo Alto, CA 94304, USA.
Cell Stem Cell. 2007 Dec 13;1(6):635-45. doi: 10.1016/j.stem.2007.10.001.
Mouse hematopoiesis is initiated by long-term hematopoietic stem cells (HSC) that differentiate into a series of multipotent progenitors that exhibit progressively diminished self-renewal ability. In human hematopoiesis, populations enriched for HSC activity have been identified, as have downstream lineage-committed progenitors, but multipotent progenitor activity has not been uniquely isolated. Previous reports indicate that human HSC are enriched in Lin-CD34+CD38- cord blood and bone marrow and express CD90. We demonstrate that the Lin-CD34+CD38- fraction of cord blood and bone marrow can be subdivided into three subpopulations: CD90+CD45RA-, CD90-CD45RA-, and CD90-CD45RA+. Utilizing in vivo transplantation studies and complementary in vitro assays, we demonstrate that the Lin-CD34+CD38-CD90+CD45RA- cord blood fraction contains HSC and isolate this activity to as few as 10 purified cells. Furthermore, we report the first prospective isolation of a population of candidate human multipotent progenitors, Lin-CD34+CD38-CD90-CD45RA- cord blood.
小鼠造血由长期造血干细胞(HSC)启动,这些干细胞分化为一系列多能祖细胞,其自我更新能力逐渐减弱。在人类造血过程中,已鉴定出富含HSC活性的细胞群体以及下游定向谱系祖细胞,但尚未独特分离出多能祖细胞活性。先前的报告表明,人类HSC在脐带血和骨髓的Lin-CD34+CD38-细胞群中富集,并表达CD90。我们证明,脐带血和骨髓的Lin-CD34+CD38-部分可细分为三个亚群:CD90+CD45RA-、CD90-CD45RA-和CD90-CD45RA+。利用体内移植研究和互补的体外分析,我们证明脐带血的Lin-CD34+CD38-CD90+CD45RA-部分含有HSC,并将这种活性分离到少至10个纯化细胞中。此外,我们首次前瞻性分离出一群候选人类多能祖细胞,即脐带血的Lin-CD34+CD38-CD90-CD45RA-。