title: GATA-3 regulates hematopoietic stem cell maintenance and cell-cycle entry.
abstract: Maintaining hematopoietic stem cell (HSC) quiescence is a critical property for the life-long generation of blood cells. Approximately 75% of cells in a highly enriched long-term repopulating HSC (LT-HSC) pool (Lin(-)Sca1(+)c-Kit(hi)CD150(+)CD48(-)) are quiescent, with only a small percentage of the LT-HSCs in cycle. Transcription factor GATA-3 is known to be vital for the development of T cells at multiple stages in the thymus and for Th2 differentiation in the peripheral organs. Although it is well documented that GATA-3 is expressed in HSCs, a role for GATA-3 in any prethymic progenitor cell has not been established. In the present study, we show that Gata3-null mutant mice generate fewer LT-HSCs and that fewer Gata3-null LT-HSCs are in cycle. Furthermore, Gata3 mutant hematopoietic progenitor cells fail to be recruited into an increased cycling state after 5-fluorouracil-induced myelosuppression. Therefore, GATA-3 is required for the maintenance of a normal number of LT-HSCs and for their entry into the cell cycle.
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, USA.
authors.forename: Chia-Jui
authors.initials: CJ
authors.lastname: Ku
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hosoya
authors.forename: Ivan
authors.initials: I
authors.lastname: Maillard
authors.forename: James Douglas
authors.initials: JD
authors.lastname: Engel
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D049109:Cell Proliferation; D050989:GATA2 Transcription Factor / Q000235:genetics; D050990:GATA3 Transcription Factor / Q000235:genetics*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006410:Hematopoiesis / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; C494712:Gata2 protein, mouse; C494748:Gata3 protein, mouse