Definitive Hematopoietic Multipotent Progenitor Cells Are Transiently Generated From Hemogenic Endothelial Cells in Human Pluripotent Stem Cells.
Definitive Hematopoietic Multipotent Progenitor Cells Are Transiently Generated From Hemogenic Endothelial Cells in Human Pluripotent Stem Cells.
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DOI：
10.1002/jcp.25199
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发表时间：
2016-05
影响因子：
5.6
通讯作者：
Wang ZZ
中科院分区：
文献类型：
--
作者：
Bai H;Liu Y;Xie Y;Hoyle DL;Brodsky RA;Cheng L;Cheng T;Wang ZZ
从人多能干细胞（hPSCs）生成功能齐全的造血多能祖细胞（MPP）具有巨大的治疗潜力，为血液疾病的治疗提供了无限的细胞来源。我们之前已经证明，来源于人造血干细胞的CD34+CD31+CD144+群体含有造血内皮祖细胞（HEPs），这些祖细胞可以产生造血细胞和内皮细胞。在这里，我们报道了一个分化系统，通过内皮单层从HEPs生成最终的造血MPP细胞。在血管生成因子存在的情况下，HEPs形成内皮单层，通过内皮-造血转化（EHT）过程产生造血簇。造血生长因子显著增强EHT。内皮单层生成的最终MPP细胞能够形成多系造血集落，产生T淋巴样细胞，并分化为去核红细胞。造血细胞从内皮单层出现是短暂的。在内皮生长条件下，长时间培养HEPs会丧失造血潜能。我们的研究表明，CD34+CD31+CD144+ HEPs通过短暂存在的造血内皮细胞产生造血MPP细胞。建立的分化系统为未来研究造血MPP细胞新生的调控因子及其在移植中的应用提供了平台。
Generation of fully functional hematopoietic multipotent progenitor (MPP) cells from human pluripotent stem cells (hPSCs) has a great therapeutic potential to provide an unlimited cell source for treatment of hematological disorders. We previously demonstrated that CD34+CD31+CD144+ population derived from hPSCs contain hemato-endothelial progenitors (HEPs) that give rise to hematopoietic and endothelial cells. Here, we report a differentiation system to generate definitive hematopoietic MPP cells from HEPs via endothelial monolayer. In the presence of angiogenic factors, HEPs formed an endothelial monolayer, from which hematopoietic clusters emerged through the process of endothelial-to-hematopoietic transition (EHT). EHT was significantly enhanced by hematopoietic growth factors. The definitive MPP cells generated from endothelial monolayer were capable of forming multilineage hematopoietic colonies, giving rise to T lymphoid cells, and differentiating into enucleated erythrocytes. Emergence of hematopoietic cells from endothelial monolayer occurred transiently. Hematopoietic potential was lost during prolonged culture of HEPs in endothelial growth conditions. Our study demonstrated that CD34+CD31+CD144+ HEPs gave rise to hematopoietic MPP cells via hemogenic endothelial cells that exist transiently. The established differentiation system provides a platform for future investigation of regulatory factors involved in de novo generation of hematopoietic MPP cells and their applications in transplantation.