GATA2 Is Dispensable for Specification of Hemogenic Endothelium but Promotes Endothelial-to-Hematopoietic Transition
| Autor: | James A. Thomson, HyunJun Kang, Walatta-Tseyon Mesquitta, Ho Sun Jung, Oleg V. Moskvin, Igor I. Slukvin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Hemangioblasts Biology Biochemistry Article endothelial-to-hematopoietic transition Cell Line 03 medical and health sciences Gene Knockout Techniques Genetics medicine GATA2 Leukocytes Humans human pluripotent stem cells Lymphocytes hemogenic endothelium lcsh:QH301-705.5 Gene Embryonic Stem Cells Hemogenic endothelium Gene Editing lcsh:R5-920 Gene Expression Profiling Hematopoietic stem cell Embryo Cell Differentiation Cell Biology hemangioblast Hematopoietic Stem Cells Embryonic stem cell hematopoiesis Cell biology GATA2 Transcription Factor Haematopoiesis 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Gene Targeting Hemangioblast lcsh:Medicine (General) Developmental Biology |
| Zdroj: | Stem Cell Reports Stem Cell Reports, Vol 11, Iss 1, Pp 197-211 (2018) |
| ISSN: | 2213-6711 |
| Popis: | Summary 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-cadherin+CD43−CD73+ non-HE or VE-cadherin+CD43−CD73– 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. Graphical Abstract Highlights • GATA2 is not required for hemogenic endothelium (HE) specification • GATA2 regulates endothelial-to-hematopoietic transition in HE • GATA2 fails to enforce hematopoietic program in non-HE • Distinct GATA2-regulated networks are established in HE and non-HE In this article, Slukvin and colleagues show that GATA2 transcription factor is dispensable for hemogenic endothelium (HE) specification and diversification. However, GATA2 is primarily needed for HE to undergo endothelial-to-hematopoietic transition. They also revealed differences in the GATA2-regulated network in HE and non-HE. |
| Databáze: | OpenAIRE |
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