GATA-3 Regulates the Self-Renewal of Long-Term Hematopoietic Stem Cells

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

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism*
  • Gene Deletion
  • Gene Expression
  • Hematopoiesis / genetics
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism*
  • Ligands
  • Mice
  • Mice, Knockout
  • Poly I-C / pharmacology
  • Protein Transport
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Toll-Like Receptors / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • GATA3 Transcription Factor
  • Ligands
  • RNA, Messenger
  • Toll-Like Receptors
  • p38 Mitogen-Activated Protein Kinases
  • Poly I-C