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Functional and molecular characterization of mouse Gata2-independent hematopoietic progenitors

Authors :
Kaimakis, P. (Polynikis)
Pater, E. (Emma) de
Eich, C. (Christina)
Solaimani Kartalaei, P. (Parham)
Kauts, M.-L. (Mari-Liis)
Vink, C.S. (Chris)
Van Der Linden, R. (Reinier)
Jaegle, M.M. (Martine)
Yokomizo, T. (Tomomasa)
Meijer, D.N. (Dies)
Dzierzak, E.A. (Elaine)
Kaimakis, P. (Polynikis)
Pater, E. (Emma) de
Eich, C. (Christina)
Solaimani Kartalaei, P. (Parham)
Kauts, M.-L. (Mari-Liis)
Vink, C.S. (Chris)
Van Der Linden, R. (Reinier)
Jaegle, M.M. (Martine)
Yokomizo, T. (Tomomasa)
Meijer, D.N. (Dies)
Dzierzak, E.A. (Elaine)
Publication Year :
2016

Abstract

The Gata2 transcription factor is a pivotal regulator of hematopoietic cell development and maintenance, highlighted by the fact that Gata2 haploinsufficiency has been identified as the cause of some familial cases of acute myelogenous leukemia/myelodysplastic syndrome and in MonoMac syndrome. Genetic deletion in mice has shown that Gata2 is pivotal to the embryonic generation of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). It functions in the embryo during endothelial cell to hematopoietic cell transition to affect hematopoietic cluster, HPC, and HSC formation. Gata2 conditional deletion and overexpression studies show the importance of Gata2 levels in hematopoiesis, during all developmental stages. Although previous studies of cell populations phenotypically enriched in HPCs and HSCs show expression of Gata2, therehasbeen nodirect study of Gata2 expressing cells during normal hematopoiesis. In this study, we generate a Gata2Venus reporter mouse model with unperturbed Gata2 expression to examine the hematopoietic function and transcriptome of Gata2 expressing and nonexpressing cells. We show that all the HSCs are Gata2 expressing. However, not allHPCs in the aorta, vitellineand umbilical arteries, and fetal liver require or express Gata2. These Gata2-independent HPCs exhibit a different functional output and genetic program, including Ras and cyclic AMP response element-binding protein pathways and other Gata factors, compared with Gata2-dependent HPCs. Our results, indicating that Gata2 is of major importance in programming toward HSC fate but not in all cells with HPC fate, have implications for current reprogramming strategies.

Details

Database :
OAIster
Notes :
Blood vol. 127 no. 11, pp. 1426-1437, English
Publication Type :
Electronic Resource
Accession number :
edsoai.ocn957101955
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1182.blood-2015-10-673749