Gata2-regulated Gfi1b expression controls endothelial programming during endothelial-to-hematopoietic transition
| Autor: | Cansu Koyunlar, Emanuele Gioacchino, Disha Vadgama, Hans de Looper, Joke Zink, Mariette N. D. ter Borg, Remco Hoogenboezem, Marije Havermans, Mathijs A. Sanders, Eric Bindels, Elaine Dzierzak, Ivo P. Touw, Emma de Pater |
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| Přispěvatelé: | Hematology, Pathology, Cell biology |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Blood advances, 7(10), 2082-2093. American Society of Hematology |
| ISSN: | 2473-9537 2473-9529 |
| Popis: | The first hematopoietic stem cells (HSCs) are formed through endothelial-to-hematopoietic transition (EHT) during embryonic development. The transcription factor GATA2 is a crucial regulator of EHT and HSC function throughout life. Because patients with GATA2 haploinsufficiency have inborn mutations, prenatal defects are likely to influence disease development. In mice, Gata2 haploinsufficiency (Gata2+/−) reduces the number and functionality of embryonic hematopoietic stem and progenitor cells (HSPCs) generated through EHT. However, the embryonic HSPC pool is heterogeneous and the mechanisms underlying this defect in Gata2+/− embryos remain unclear. Here, we investigated whether Gata2 haploinsufficiency selectively affects a cellular subset undergoing EHT. We showed that Gata2+/− HSPCs initiate, but cannot fully activate, hematopoietic programming during EHT. In addition, due to the reduced activity of the endothelial repressor Gfi1b, Gata2+/− HSPCs cannot repress endothelial identity to complete maturation. Finally, we showed that hematopoietic-specific induction of gfi1b could restore HSC production in gata2b-null (gata2b−/−) zebrafish embryos. This study illustrates the pivotal role of Gata2 in the regulation of the transcriptional network governing HSPC identity throughout the EHT. |
| Databáze: | OpenAIRE |
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