GATA2 对于造血内皮细胞的特化不是必需的，但促进了内皮细胞向造血细胞的转变。
GATA2 Is Dispensable for Specification of Hemogenic Endothelium but Promotes Endothelial-to-Hematopoietic Transition.
机构信息
Wisconsin National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, WI 53715, USA.
Morgridge Institute for Research, 330 N. Orchard Street, Madison, WI 53715, USA; Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53707-7365, USA; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
出版信息
Stem Cell Reports. 2018 Jul 10;11(1):197-211. doi: 10.1016/j.stemcr.2018.05.002. Epub 2018 May 31.
The transcriptional factor GATA2 is required for blood and hematopoietic stem cell formation during the hemogenic endothelium (HE) stage of development in the embryo. However, it is unclear if GATA2 controls HE lineage specification or if it solely regulates endothelial-to-hematopoietic transition (EHT). To address this problem, we innovated a unique system, which involved generating GATA2 knockout human embryonic stem cell (hESC) lines with conditional GATA2 expression (iG2 hESCs). We demonstrated that GATA2 activity is not required for VE-cadherinCD43CD73 non-HE or VE-cadherinCD43CD73 HE generation and subsequent HE diversification into DLL4 arterial and DLL4 non-arterial lineages. However, GATA2 is primarily needed for HE to undergo EHT. Forced expression of GATA2 in non-HE failed to induce blood formation. The lack of GATA2 requirement for generation of HE and non-HE indicates the critical role of GATA2-independent pathways in specification of these two distinct endothelial lineages.
转录因子 GATA2 是胚胎造血内皮（HE）阶段血液和造血干细胞形成所必需的。然而，目前尚不清楚 GATA2 是否控制 HE 谱系特化，还是仅调节内皮向造血转变（EHT）。为了解决这个问题，我们创新了一种独特的系统，包括生成具有条件 GATA2 表达（iG2 hESCs）的 GATA2 敲除人类胚胎干细胞（hESC）系。我们证明 GATA2 活性对于 VE-cadherinCD43CD73 非 HE 或 VE-cadherinCD43CD73 HE 的生成以及随后的 HE 多样化为 DLL4 动脉和 DLL4 非动脉谱系不是必需的。然而，GATA2 主要是 HE 进行 EHT 所必需的。在非 HE 中强制表达 GATA2 不能诱导血液形成。缺乏 GATA2 对 HE 和非 HE 的生成要求表明 GATA2 独立途径在这两个不同内皮谱系的特化中起着关键作用。
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