Essential role for Gata2 in modulating lineage output from hematopoietic stem cells in zebrafish
Autor: | Cansu Koyunlar, Hans de Looper, Dennis Bosch, Rui Monteiro, Emma de Pater, Joke Zink, Ivo P. Touw, Christopher B. Mahony, Madelon de Jong, Martin E. van Royen, Tomasz Dobrzycki, Eric Bindels, Remco Hoogenboezem, Paulina M. H. van Strien, Kirsten Gussinklo, Pim J. French, Emanuele Gioacchino |
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Přispěvatelé: | Hematology, Pathology, Neurology |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Myeloid Lineage (genetic) Hematopoiesis and Stem Cells Cellular differentiation Biology Monocytes Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Progenitor cell Zebrafish Cell Differentiation Hematology Zebrafish Proteins Hematopoietic Stem Cells biology.organism_classification Embryonic stem cell Hematopoiesis Cell biology GATA2 Transcription Factor Haematopoiesis 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Stem cell |
Zdroj: | Blood advances, 5(13), 2687-2700. American Society of Hematology Blood Adv |
ISSN: | 2473-9529 |
Popis: | The differentiation of hematopoietic stem cells (HSCs) is tightly controlled to ensure a proper balance between myeloid and lymphoid cell output. GATA2 is a pivotal hematopoietic transcription factor required for generation and maintenance of HSCs. GATA2 is expressed throughout development, but because of early embryonic lethality in mice, its role during adult hematopoiesis is incompletely understood. Zebrafish contains 2 orthologs of GATA2: Gata2a and Gata2b, which are expressed in different cell types. We show that the mammalian functions of GATA2 are split between these orthologs. Gata2b-deficient zebrafish have a reduction in embryonic definitive hematopoietic stem and progenitor cell (HSPC) numbers, but are viable. This allows us to uniquely study the role of GATA2 in adult hematopoiesis. gata2b mutants have impaired myeloid lineage differentiation. Interestingly, this defect arises not in granulocyte-monocyte progenitors, but in HSPCs. Gata2b-deficient HSPCs showed impaired progression of the myeloid transcriptional program, concomitant with increased coexpression of lymphoid genes. This resulted in a decrease in myeloid-programmed progenitors and a relative increase in lymphoid-programmed progenitors. This shift in the lineage output could function as an escape mechanism to avoid a block in lineage differentiation. Our study helps to deconstruct the functions of GATA2 during hematopoiesis and shows that lineage differentiation flows toward a lymphoid lineage in the absence of Gata2b. |
Databáze: | OpenAIRE |
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