GATA-3 regulates hematopoietic stem cell maintenance and cell-cycle entry

• Published in: Blood Vol. 119; no. 10; pp. 2242 - 2251
• Main Authors: Ku, Chia-Jui, Hosoya, Tomonori, Maillard, Ivan, Engel, James Douglas
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 08.03.2012; Americain Society of Hematology; American Society of Hematology
• Subjects: Animals; Biological and medical sciences; Cell Cycle - genetics; Cell Proliferation; GATA2 Transcription Factor - genetics; GATA3 Transcription Factor - genetics; Gene Expression Regulation; Gene Regulatory Networks; Hematologic and hematopoietic diseases; Hematopoiesis - genetics; Hematopoiesis and Stem Cells; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Reverse Transcriptase Polymerase Chain Reaction; Transcription factor GATA3; Hematopoietic cell; Hematology; Stem cell; Cell cycle
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-07-366070

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-KithiCD150+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.