MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, Scotland, UK.
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, Scotland, UK.
Stem Cell Reports. 2014 Mar 27;2(4):449-56. doi: 10.1016/j.stemcr.2014.02.004. eCollection 2014 Apr 8.
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(-/lo)CD45RA(-). 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.
在各种脊椎动物物种中，背主动脉（Ao）是成年造血干细胞（HSCs）规范的部位。人们观察到，必需的造血转录因子的上调和特定的主动脉内造血细胞簇的形成主要发生在 Ao 的腹侧域（AoV）。在小鼠中，第一个 HSCs 出现在 AoV。在这里，我们证明在人类胚胎中，第一个明确的 HSCs 也不对称地出现，并定位于 AoV，这因此确定了发育人类 HSCs 的功能小生境。通过使用磁性细胞分离和异种移植，我们显示第一个人类 HSCs 是 CD34(+)VE-cadherin(+)CD45(+)C-KIT(+)THY-1(+)Endoglin(+)RUNX1(+)CD38(-/lo)CD45RA(-)。该群体几乎包含所有定向造血祖细胞，并且在 Ao 的背侧域（AoD）和泌尿生殖嵴（UGRs）中代表性不足。本研究为分析胚胎人类 HSCs 规范的分子机制提供了基础。
