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Nat Immunol. 2013 Oct;14(10):1037-44. doi: 10.1038/ni.2692. Epub 2013 Aug 25.

GATA-3 regulates the self-renewal of long-term hematopoietic stem cells.

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1] Ontario Cancer Institute, University Health Network, Toronto, Canada. [2] Department of Medical Biophysics, University of Toronto, Toronto, Canada.


The transcription factor GATA-3 is expressed and required for differentiation and function throughout the T lymphocyte lineage. Despite evidence it may also be expressed in multipotent hematopoietic stem cells (HSCs), any role for GATA-3 in these cells has remained unclear. Here we found GATA-3 was in the cytoplasm in quiescent long-term stem cells from steady-state bone marrow but relocated to the nucleus when HSCs cycled. Relocation depended on signaling via the mitogen-activated protein kinase p38 and was associated with a diminished capacity for long-term reconstitution after transfer into irradiated mice. Deletion of Gata3 enhanced the repopulating capacity and augmented the self-renewal of long-term HSCs in cell-autonomous fashion without affecting the cell cycle. Our observations position GATA-3 as a regulator of the balance between self-renewal and differentiation in HSCs that acts downstream of the p38 signaling pathway.

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