McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada.
Cell Rep. 2012 Dec 27;2(6):1722-35. doi: 10.1016/j.celrep.2012.11.003. Epub 2012 Dec 7.
The efficient generation of hematopoietic stem cells from human pluripotent stem cells is dependent on the appropriate specification of the definitive hematopoietic program during differentiation. In this study, we used T lymphocyte potential to track the onset of definitive hematopoiesis from human embryonic and induced pluripotent stem cells differentiated with specific morphogens in serum- and stromal-free cultures. We show that this program develops from a progenitor population with characteristics of hemogenic endothelium, including the expression of CD34, VE-cadherin, GATA2, LMO2, and RUNX1. Along with T cells, these progenitors display the capacity to generate myeloid and erythroid cells. Manipulation of Activin/Nodal signaling during early stages of differentiation revealed that development of the definitive hematopoietic progenitor population is not dependent on this pathway, distinguishing it from primitive hematopoiesis. Collectively, these findings demonstrate that it is possible to generate T lymphoid progenitors from pluripotent stem cells and that this lineage develops from a population whose emergence marks the onset of human definitive hematopoiesis.
从人类多能干细胞高效生成造血干细胞依赖于在分化过程中适当规范确定性造血程序。在这项研究中，我们使用 T 淋巴细胞潜能来追踪源自人胚胎和诱导多能干细胞的确定性造血的起始，这些细胞在无血清和基质的培养中使用特定的形态发生素来分化。我们表明，该程序源自具有造血内皮特征的祖细胞群体，包括表达 CD34、VE-钙黏蛋白、GATA2、LMO2 和 RUNX1。与 T 细胞一起，这些祖细胞具有生成髓样细胞和红细胞的能力。在分化的早期阶段对激活素/Nodal 信号的操作表明，确定性造血祖细胞群体的发育不依赖于该途径，这使其与原始造血区分开来。总的来说，这些发现表明有可能从多能干细胞中生成 T 淋巴祖细胞，并且该谱系是从一个群体中发育而来的，该群体的出现标志着人类确定性造血的开始。
