The RUNX1b Isoform Defines Hemogenic Competency in Developing Human Endothelial Cells.
The RUNX1b Isoform Defines Hemogenic Competency in Developing Human Endothelial Cells.
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DOI：
10.3389/fcell.2021.812639
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发表时间：
2021
影响因子：
5.5
通讯作者：
Kouskoff V
中科院分区：
文献类型：
--
作者：
Menegatti S;Potts B;Garcia-Alegria E;Paredes R;Lie-A-Ling M;Lacaud G;Kouskoff V
转录因子RUNX1是血细胞规格的主要调节因子。在胚胎发生过程中，造血祖细胞最初是由造血内皮通过由RUNX1控制的内皮到造血的过渡产生的。一些研究已经解剖了RUNX1亚型在小鼠造血开始时的表达模式和作用，但RUNX1亚型在人类造血开始时的确切表达模式和表达RUNX1的细胞的生物学输出仍然不完全清楚。在这里，我们使用RUNX1b:VENUS RUNX1c:TOMATO人胚胎干细胞系来研究这些问题，该细胞系允许通过流式细胞术进行多参数单细胞分辨率，并分离表达RUNX1b的细胞进行进一步分析。我们的数据揭示了两种RUNX1亚型的顺序表达，其中RUNX1b首先在内皮细胞亚群中表达，并在内皮细胞向造血细胞过渡期间表达，而RUNX1c仅在完全指定的血细胞中表达。此外，我们的数据显示，RUNX1b标志着内皮细胞具有造血潜能，并且RUNX1b的表达水平以剂量依赖的方式决定了造血能力。我们的数据共同揭示了RUNX1亚型在人类血液规格开始时的表达动态，并确定RUNX1b亚型是已知最早的血液生成能力标记。
The transcription factor RUNX1 is a master regulator of blood cell specification. During embryogenesis, hematopoietic progenitors are initially generated from hemogenic endothelium through an endothelium-to-hematopoietic transition controlled by RUNX1. Several studies have dissected the expression pattern and role of RUNX1 isoforms at the onset of mouse hematopoiesis, however the precise pattern of RUNX1 isoform expression and biological output of RUNX1-expressing cells at the onset of human hematopoiesis is still not fully understood. Here, we investigated these questions using a RUNX1b:VENUS RUNX1c:TOMATO human embryonic stem cell line which allows multi-parameter single cell resolution via flow cytometry and isolation of RUNX1b-expressing cells for further analysis. Our data reveal the sequential expression of the two RUNX1 isoforms with RUNX1b expressed first in a subset of endothelial cells and during the endothelial to hematopoietic transition while RUNX1c only becomes expressed in fully specified blood cells. Furthermore, our data show that RUNX1b marks endothelial cells endowed with hemogenic potential and that RUNX1b expression level determines hemogenic competency in a dose-dependent manner. Together our data reveal the dynamic of RUNX1 isoforms expression at the onset of human blood specification and establish RUNX1b isoform as the earliest known marker for hemogenic competency.
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影响因子：
5.9
作者：
Garcia-Alegria E;Menegatti S;Fadlullah MZH;Menendez P;Lacaud G;Kouskoff V
通讯作者：
Kouskoff V
影响因子：
--
作者：
Garcia-Alegria E;Potts B;Menegatti S;Kouskoff V
通讯作者：
Kouskoff V
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：
Vodyanik, Maxim A.;Thomson, James A.;Slukvin, Igor I.
通讯作者：
Slukvin, Igor I.
影响因子：
21.3
作者：
Ditadi A;Sturgeon CM;Tober J;Awong G;Kennedy M;Yzaguirre AD;Azzola L;Ng ES;Stanley EG;French DL;Cheng X;Gadue P;Speck NA;Elefanty AG;Keller G
通讯作者：
Keller G