GATA2 Is Dispensable for Specification of Hemogenic Endothelium but Promotes Endothelial-to-Hematopoietic Transition
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 tra...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-07-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671118302194 |
| _version_ | 1818215251856850944 |
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| author | HyunJun Kang Walatta-Tseyon Mesquitta Ho Sun Jung Oleg V. Moskvin James A. Thomson Igor I. Slukvin |
| author_facet | HyunJun Kang Walatta-Tseyon Mesquitta Ho Sun Jung Oleg V. Moskvin James A. Thomson Igor I. Slukvin |
| author_sort | HyunJun Kang |
| collection | DOAJ |
| description | 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. : 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. Keywords: GATA2, human pluripotent stem cells, hematopoiesis, endothelial-to-hematopoietic transition, hemogenic endothelium, hemangioblast, hematopoietic stem cells |
| first_indexed | 2024-12-12T06:33:07Z |
| format | Article |
| id | doaj.art-589549e31a6d41479885349dee86448f |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-12T06:33:07Z |
| publishDate | 2018-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-589549e31a6d41479885349dee86448f2022-12-22T00:34:32ZengElsevierStem Cell Reports2213-67112018-07-01111197211GATA2 Is Dispensable for Specification of Hemogenic Endothelium but Promotes Endothelial-to-Hematopoietic TransitionHyunJun Kang0Walatta-Tseyon Mesquitta1Ho Sun Jung2Oleg V. Moskvin3James A. Thomson4Igor I. Slukvin5Wisconsin National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, WI 53715, USAWisconsin National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, WI 53715, USAWisconsin National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, WI 53715, USAWisconsin National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, WI 53715, USAMorgridge 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, USAWisconsin National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, 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 Pathology and Laboratory Medicine, University of Wisconsin Medical School, 600 Highland Avenue, Madison, WI 53792, USA; Corresponding authorSummary: 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. : 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. Keywords: GATA2, human pluripotent stem cells, hematopoiesis, endothelial-to-hematopoietic transition, hemogenic endothelium, hemangioblast, hematopoietic stem cellshttp://www.sciencedirect.com/science/article/pii/S2213671118302194 |
| spellingShingle | HyunJun Kang Walatta-Tseyon Mesquitta Ho Sun Jung Oleg V. Moskvin James A. Thomson Igor I. Slukvin GATA2 Is Dispensable for Specification of Hemogenic Endothelium but Promotes Endothelial-to-Hematopoietic Transition Stem Cell Reports |
| title | GATA2 Is Dispensable for Specification of Hemogenic Endothelium but Promotes Endothelial-to-Hematopoietic Transition |
| title_full | GATA2 Is Dispensable for Specification of Hemogenic Endothelium but Promotes Endothelial-to-Hematopoietic Transition |
| title_fullStr | GATA2 Is Dispensable for Specification of Hemogenic Endothelium but Promotes Endothelial-to-Hematopoietic Transition |
| title_full_unstemmed | GATA2 Is Dispensable for Specification of Hemogenic Endothelium but Promotes Endothelial-to-Hematopoietic Transition |
| title_short | GATA2 Is Dispensable for Specification of Hemogenic Endothelium but Promotes Endothelial-to-Hematopoietic Transition |
| title_sort | gata2 is dispensable for specification of hemogenic endothelium but promotes endothelial to hematopoietic transition |
| url | http://www.sciencedirect.com/science/article/pii/S2213671118302194 |
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