Functional and molecular characterization of mouse Gata2-independent hematopoietic progenitors.

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, 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 nonexpressing 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 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.

• Authors: 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
• Journal: Blood (Blood) Vol. 127 Issue 11 Pg. 1426-37 (Mar 17 2016) ISSN: 1528-0020 [Electronic] United States
• PMID: 26834239 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 by The American Society of Hematology.

Chemical References

• Bacterial Proteins
• GATA2 Transcription Factor
• Gata2 protein, mouse
• Luminescent Proteins
• yellow fluorescent protein, Bacteria

Topics

• Animals
• Aorta (cytology, embryology)
• Bacterial Proteins (analysis, genetics)
• Cell Lineage
• Cells, Cultured
• Cellular Reprogramming Techniques
• GATA2 Transcription Factor (deficiency, genetics, physiology)
• Gene Expression Regulation, Developmental
• Genes, Reporter
• Genetic Vectors (genetics)
• Hematopoiesis (physiology)
• Hematopoietic Stem Cell Transplantation
• Hematopoietic Stem Cells (classification, cytology, physiology)
• Liver (cytology, embryology)
• Luminescent Proteins (analysis, genetics)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Transcriptome
• Transgenes
• Umbilical Arteries (cytology, embryology)