Functional and molecular characterization of mouse Gata2-independent hematopoietic progenitors

Polynikis Kaimakis, Emma de Pater, Christina Eich, Parham Solaimani Kartalaei, Mari-Liis Kauts, Chris S. Vink, Reinier van der Linden, Martine Jaegle, Tomomasa Yokomizo, Dies Meijer, Elaine Dzierzak

Research output: Contribution to journalArticlepeer-review

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 AML/MDS and in MonoMac syndrome. Genetic deletion in mice has shown that Gata2 is pivotal to the embryonic generation of hematopoietic stem cells (HSC) and hematopoietic progenitor cells (HPC). It functions in the embryo during endothelial cell to hematopoietic cell transition (EHT) 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, there has been no direct 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 non-expressing cells. We show that all the HSCs are Gata2 expressing. However, not all HPCs in the aorta, vitelline and umbilical arteries and fetal liver require or express Gata2. These Gata2-independent HPCs exhibit a different functional output and genetic program, including Ras and CREB pathways and other Gata factors, when compared to Gata2-dependent HPCs. Our results, indicating that Gata2 is of major importance in programming towards HSC fate but not in all cells with HPC fate, have implications for current reprogramming strategies.

Original languageEnglish
Pages (from-to)1426-1437
Number of pages12
JournalBlood
Volume127
Issue number11
Early online date1 Feb 2016
DOIs
Publication statusPublished - 17 Mar 2016

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