Identification of the niche and phenotype of the first human hematopoietic stem cells.
Identification of the niche and phenotype of the first human hematopoietic stem cells.
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DOI：
10.1016/j.stemcr.2014.02.004
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发表时间：
2014-04-08
影响因子：
5.9
通讯作者：
Medvinsky, Alexander
中科院分区：
文献类型：
--
作者：
Ivanovs, Andrejs;Rybtsov, Stanislav;Anderson, Richard A.;Turner, Marc L.;Medvinsky, Alexander
在各种脊椎动物中，背主动脉 (Ao) 是成体造血干细胞 (HSC) 的特化部位。据观察，必需造血转录因子的上调和特定主动脉内造血细胞簇的形成主要发生在 Ao (AoV) 的腹侧区域。在小鼠中，第一个 HSC 出现在 AoV 中。在这里，我们证明，在人类胚胎中，第一个明确的 HSC 也是不对称出现的，并且定位于 AoV，从而确定了人类 HSC 发育的功能位。使用磁性细胞分离和异种移植，我们证明第一个人类 HSC 是 CD34+VE-cadherin+CD45+C-KIT+THY-1+Endoglin+RUNX1+CD38−/loCD45RA−。该群体几乎拥有所有定向造血祖细胞，并且在 Ao (AoD) 背侧域和泌尿生殖嵴 (UGR) 中代表性不足。本研究为分析支持人类 HSC 胚胎规范的分子机制奠定了基础。第一个人类 HSC 在 AoV 中发育 这些细胞是 CD34+VE-cadherin+CD45+C-KIT+THY-1+Endoglin+RUNX1+CD38−/loCD45RA− VE-cadherin 是 AGM 区域 HSC 功能上重要的表面抗原 人类造血干细胞 (HSC) 首先出现在主动脉-性腺-中肾 (AGM) 区域。 Medvinsky 及其同事证明，第一个人类 HSC 不对称地出现在背主动脉 (AoV) 的腹侧区域，并且为 CD34+VE-cadherin+CD45+C-KIT+THY-1+Endoglin+RUNX1+CD38−/loCD45RA−。这项研究为人类发育过程中早期 HSC 规范的进一步机制分析奠定了基础。
In various vertebrate species, the dorsal aorta (Ao) is the site of specification of adult hematopoietic stem cells (HSCs). It has been observed that the upregulation of essential hematopoietic transcription factors and the formation of specific intra-aortic hematopoietic cell clusters occur predominantly in the ventral domain of the Ao (AoV). In the mouse, the first HSCs emerge in the AoV. Here, we demonstrate that in the human embryo the first definitive HSCs also emerge asymmetrically and are localized to the AoV, which thus identifies a functional niche for developing human HSCs. Using magnetic cell separation and xenotransplantations, we show that the first human HSCs are CD34+VE-cadherin+CD45+C-KIT+THY-1+Endoglin+RUNX1+CD38−/loCD45RA−. This population harbors practically all committed hematopoietic progenitors and is underrepresented in the dorsal domain of the Ao (AoD) and urogenital ridges (UGRs). The present study provides a foundation for analysis of molecular mechanisms underpinning embryonic specification of human HSCs. The first human HSCs develop in the AoV These cells are CD34+VE-cadherin+CD45+C-KIT+THY-1+Endoglin+RUNX1+CD38−/loCD45RA− VE-cadherin is a functionally important surface antigen of AGM region HSCs Human hematopoietic stem cells (HSCs) first appear in the aorta-gonad-mesonephros (AGM) region. Medvinsky and colleagues demonstrate that the first human HSCs emerge asymmetrically in the ventral domain of the dorsal aorta (AoV) and are CD34+VE-cadherin+CD45+C-KIT+THY-1+Endoglin+RUNX1+CD38−/loCD45RA−. This study provides a foundation for further mechanistic analysis of early HSC specification during human development.
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影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
影响因子：
20.3
作者：
Marshall, CJ;Kinnon, C;Thrasher, AJ
通讯作者：
Thrasher, AJ
DOI：
10.1073/pnas.89.7.2804
发表时间：
1992-04-01
影响因子：
11.1
作者：
BAUM, CM;WEISSMAN, IL;PEAULT, B
通讯作者：
PEAULT, B
DOI：
10.1073/pnas.0402270102
发表时间：
2005-01-04
影响因子：
11.1
作者：
Bertrand, JY;Giroux, S;Cumano, A
通讯作者：
Cumano, A
DOI：
10.1073/pnas.202614899
发表时间：
2002-11-26
影响因子：
11.1
作者：
Chen, CZ;Li, M;Lodish, HF
通讯作者：
Lodish, HF