Highly potent human hematopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region.
Highly potent human hematopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region.
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DOI：
10.1084/jem.20111688
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发表时间：
2011-11-21
期刊：
影响因子：
--
通讯作者：
Medvinsky A
中科院分区：
文献类型：
--
作者：
Ivanovs A;Rybtsov S;Welch L;Anderson RA;Turner ML;Medvinsky A
人HSC首先出现在胚胎背主动脉中，并且仅稍后出现在卵黄囊、肝脏和胎盘中;单个人AGM区域HSC可以产生至少300个可再移植到次级受体小鼠中的子代HSC。造血干细胞（HSCs）在胚胎发生过程中出现，并在成年生物体中维持造血。关于人类HSC的胚胎发育知之甚少。我们证明，人类造血干细胞首先出现在AGM区域，特别是在背主动脉，后来才出现在卵黄囊，肝脏和胎盘。移植到免疫缺陷小鼠的AGM区细胞提供长期高水平的多系造血重建。人AGM区HSC虽然数量较少，但表现出非常高的自我更新潜力。来自AGM区域的单个HSC在原代受体中产生至少300个子HSC，其散布在整个受体骨髓中并且可再移植。这些发现突出了最早期人类HSC的巨大再生潜力，并为再生医学目的从多能干细胞体外生成HSC设定了新标准。
Human HSCs appear first in the embryonic dorsal aorta, and only later in the yolk sac, liver, and placenta; a single human AGM region HSC can generate at least 300 daughter HSCs that are retransplantable into secondary recipient mice. Hematopoietic stem cells (HSCs) emerge during embryogenesis and maintain hematopoiesis in the adult organism. Little is known about the embryonic development of human HSCs. We demonstrate that human HSCs emerge first in the aorta-gonad-mesonephros (AGM) region, specifically in the dorsal aorta, and only later appear in the yolk sac, liver, and placenta. AGM region cells transplanted into immunodeficient mice provide long-term high level multilineage hematopoietic repopulation. Human AGM region HSCs, although present in low numbers, exhibit a very high self-renewal potential. A single HSC derived from the AGM region generates at least 300 daughter HSCs in primary recipients, which disseminate throughout the entire recipient bone marrow and are retransplantable. These findings highlight the vast regenerative potential of the earliest human HSCs and set a new standard for in vitro generation of HSCs from pluripotent stem cells for the purpose of regenerative medicine.
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