Gata2 noncoding genetic variation as a determinant of hematopoietic stem/progenitor cell mobilization efficiency.

ABSTRACT: Germline genetic variants alter the coding and enhancer sequences of GATA2, which encodes a master regulator of hematopoiesis. The conserved murine Gata2 enhancer (+9.5) promotes hematopoietic stem cell (HSC) genesis during embryogenesis. Heterozygosity for a single-nucleotide Ets motif variant in the human enhancer creates a bone marrow failure and acute myeloid leukemia predisposition termed GATA2 deficiency syndrome. The homozygous murine variant attenuates chemotherapy- and transplantation-induced hematopoietic regeneration, hematopoietic stem and progenitor cell (HSPC) response to inflammation, and HSPC mobilization with the therapeutic mobilizer granulocyte colony-stimulating factor (G-CSF). Because a Gata2 +9.5 variant attenuated G-CSF-induced HSPC expansion and mobilization, and HS

SUBMITTER: Soukup AA 

PROVIDER: S-EPMC10761364 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature