T Lymphocyte Potential Marks the Emergence of Definitive Hematopoietic Progenitors in Human Pluripotent Stem Cell Differentiation Cultures
T Lymphocyte Potential Marks the Emergence of Definitive Hematopoietic Progenitors in Human Pluripotent Stem Cell Differentiation Cultures
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DOI：
10.1016/j.celrep.2012.11.003
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发表时间：
2012-12-01
期刊：
影响因子：
8.8
通讯作者：
Keller, Gordon
中科院分区：
文献类型：
--
作者：
Kennedy, Marion;Awong, Geneve;Keller, Gordon
从人类多能干细胞有效地生成造血干细胞依赖于分化过程中明确的造血程序的适当规范。在这项研究中，我们使用T淋巴细胞电位来追踪人类胚胎和诱导多能干细胞在无血清和无基质培养中分化成特定形态因子的最终造血的开始。我们发现这个程序是从一个具有造血内皮特征的祖细胞群发展而来的，包括CD34、VE-cadherin、GATA2、LMO2和RUNX1的表达。与T细胞一起，这些祖细胞显示出产生髓细胞和红细胞的能力。在分化的早期阶段对激活素/节点信号的操纵表明，最终造血祖群体的发育不依赖于这一途径，这与原始造血不同。总的来说，这些发现表明，从多能干细胞中产生T淋巴样祖细胞是可能的，并且这一谱系是从一个群体中发展而来的，这个群体的出现标志着人类最终造血的开始。
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.