Cerdan Chantal, Bhatia Mickie
McMaster Stem Cell and Cancer Research Institute (SCC-RI), Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
Int J Dev Biol. 2010;54(6-7):955-63. doi: 10.1387/ijdb.103067cc.
Human pluripotent stem cells (PSCs) derived from a number of different sources, including reprogrammed adult somatic cells, provide a powerful cellular system to study signaling pathways implicated in cell fate decisions, and generate new sources of cells for regenerative medicine. To realize this potential, it is essential to control the direction and efficiency of human PSC differentiation. Although Notch, Wnt and Hedgehog (HH) signaling pathways have been implicated in the self-renewal/proliferation of hematopoietic stem/progenitor cells, both in vitro and in vivo, their roles in differentiation processes remain poorly explored. This review describes the role(s) of these pathways in the adult and embryonic hematopoietic system of mice and humans, with a particular emphasis on our recent studies on the hematopoietic development of human embryonic stem cells (hESCs). Understanding the individual and collective contributions of Notch, Wnt and HH signaling to the initial development of hematopoiesis is critical for achieving successful ex vivo expansion and differentiation of hematopoietic stem cells (HSCs) from human PSCs that will retain bona fide function comparable to adult-derived HSCs.
源自多种不同来源（包括重编程的成人体细胞）的人类多能干细胞（PSC），为研究与细胞命运决定相关的信号通路提供了一个强大的细胞系统，并为再生医学产生新的细胞来源。为了实现这一潜力，控制人类PSC分化的方向和效率至关重要。尽管Notch、Wnt和Hedgehog（HH）信号通路在体外和体内均与造血干/祖细胞的自我更新/增殖有关，但其在分化过程中的作用仍未得到充分探索。本综述描述了这些通路在小鼠和人类的成体及胚胎造血系统中的作用，特别强调了我们最近对人类胚胎干细胞（hESC）造血发育的研究。了解Notch、Wnt和HH信号对造血初始发育的个体和集体贡献，对于成功实现从人类PSC体外扩增和分化出具有与成人来源HSC相当的真实功能的造血干细胞（HSC）至关重要。
