Gata2 19.5 enhancer regulates adult hematopoietic stem cell self-renewal and T-cell development

Xiaona You, Yun Zhou, Yuan I. Chang, Guangyao Kong, Erik A. Ranheim, Kirby D. Johnson, Alexandra A. Soukup, Emery H. Bresnick, Jing Zhang*

*此作品的通信作者

研究成果: Article同行評審

摘要

Mammalian GATA2 gene encodes a dual zinc finger transcription factor, which is essential for hematopoietic stem cell (HSC) generation in the aorta, gonad, mesonephros (AGM) region, HSC self-renewal, and specification of progenitor cell fates. Previously, we demonstrated that Gata2 expression in AGM is controlled by its intronic 19.5 enhancer. Gata2 19.5 deficiency removes the E-box motif and the GATA site and depletes fetal liver HSCs. However, whether this enhancer has an essential role in regulating adult hematopoiesis has not been established. Here, we evaluate Gata2 19.5 enhancer function in adult hematopoiesis. 19.51/2 bone marrow cells displayed reduced T cell reconstitution in a competitive transplant assay. Donor-derived analysis demonstrated a previously unrecognized function of the 19.5 enhancer in T cell development at the lymphoid-primed multipotent progenitor stage. Moreover, 19.51/2 adult HSCs displayed increased apoptosis and reduced long-term self-renewal capability in comparison with wild-type (WT) HSCs. These phenotypes were more moderate than those of Gata21/2 HSCs. Consistent with the phenotypic characterization, Gata2 expression in 19.51/2 LSKs was moderately higher than that in Gata21/2 LSKs, but lower than that in WT LSKs. Our data suggest that 19.5 deficiency compromises, without completely abrogating, Gata2 expression in adult HSCs.

原文English
頁(從 - 到)1095-1099
頁數5
期刊Blood advances
6
發行號4
DOIs
出版狀態Published - 22 2月 2022

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