Effects of in vivo deletion of GATA2 in bone marrow stromal cells.

The bone marrow (BM) microenvironment comprises multiple stem cell niches derived from BM mesenchymal stem cells (MSCs). Previous in vitro analyses have suggested that transcription factor GATA2 plays an important role in adipocyte differentiation of BM-MSCs and in hematopoietic support, but the role of GATA2 in vivo remains unknown. We evaluated GATA2 effects in BM-MSCs in vivo. Expression profiling analysis of Gata2-knockout Ter119-CD45- mesenchymal stromal cells obtained from compact bone from tamoxifen-treated Gata2 conditional knockout mice (Gata2f/f/ER-Cre mice) revealed upregulation of 110 genes and downregulation of 141 genes by a factor of 2. Moreover, gene ontology analysis revealed significant enrichment of genes involved in cell adhesion and chemotaxis. We did not find any phenotypic changes when Gata2 was deleted with BM-MSC-related gene promoters, such as Nestin, Prx1, and Lepr, except for a significant decrease in the colony number of Gata2f/f/Prx1-Cre mice. There was a significant decrease in the percentage of the common myeloid progenitor fraction when Gata2 was deleted in all BM cells, except hematopoietic cells after normal BM cells were transplanted into irradiated Gata2f/f/ER-Cre mice with Gata2 subsequently knocked out by tamoxifen administration. In conclusion, GATA2 could affect the function of BM-MSCs in vivo, presumably by regulating the expression of extracellular signals. Copyright © 2017 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Citation

Shin Hasegawa, Tohru Fujiwara, Yoko Okitsu, Hiroki Kato, Yuki Sato, Noriko Fukuhara, Yasushi Onishi, Ritsuko Shimizu, Masayuki Yamamoto, Hideo Harigae. Effects of in vivo deletion of GATA2 in bone marrow stromal cells. Experimental hematology. 2017 Dec;56:31-45.e2

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PMID: 28866324

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