Division of Stem Cell and Developmental Biology, Campbell Family Institute for Cancer Research/Ontario Cancer Institute, Toronto, Ontario, Canada.
Science. 2011 Jul 8;333(6039):218-21. doi: 10.1126/science.1201219.
Lifelong blood cell production is dependent on rare hematopoietic stem cells (HSCs) to perpetually replenish mature cells via a series of lineage-restricted intermediates. Investigating the molecular state of HSCs is contingent on the ability to purify HSCs away from transiently engrafting cells. We demonstrated that human HSCs remain infrequent, using current purification strategies based on Thy1 (CD90) expression. By tracking the expression of several adhesion molecules in HSC-enriched subsets, we revealed CD49f as a specific HSC marker. Single CD49f(+) cells were highly efficient in generating long-term multilineage grafts, and the loss of CD49f expression identified transiently engrafting multipotent progenitors (MPPs). The demarcation of human HSCs and MPPs will enable the investigation of the molecular determinants of HSCs, with a goal of developing stem cell-based therapeutics.
终身的血细胞生成依赖于稀有造血干细胞（HSCs），通过一系列谱系限制的中间产物不断补充成熟细胞。研究 HSCs 的分子状态取决于能否将 HSCs 从短暂植入的细胞中纯化出来。我们证明，目前基于 Thy1（CD90）表达的纯化策略，人类 HSCs 仍然很少见。通过跟踪 HSC 富集亚群中几种粘附分子的表达，我们发现 CD49f 是 HSC 的特异性标记物。单个 CD49f(+)细胞在生成长期多谱系移植物方面非常有效，而 CD49f 表达的丧失则鉴定出了短暂植入的多能祖细胞（MPP）。人 HSCs 和 MPPs 的划分将能够研究 HSCs 的分子决定因素，从而开发基于干细胞的治疗方法。
