E2A proteins maintain the hematopoietic stem cell pool and promote the maturation of myelolymphoid and myeloerythroid progenitors

Craig L. Semerad, Elinore M. Mercer, Matthew A. Inlay, Irving L. Weissman, Cornelis Murre

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Hematopoiesis is a tightly controlled process maintained by a small pool of hematopoietic stem cells (HSCs). Here, we demonstrate that the LT-HSC, MPP, premegakaryocytic/erythroid, Pre CFU-E, Pre GM, MkP, and granulocyte-macrophage compartments were all significantly reduced in E2A-deficient bone marrow. Despite a severe depletion of erythroid progenitors, the erythrocyte and megakaryocyte compartments were equivalent in E2A-deficient bone marrow as compared with wild-type mice. E2A-deficient HSCs also failed to efficiently maintain the HSC pool on serial transplantation, and we demonstrate that the E2A proteins regulate cell cycle progression of HSCs by regulating the expression of p21Cip1, p27Kip1, and the thrombopoietin receptor, known regulators of HSC self-renewal activity. Based on these observations, we propose that the E2A proteins promote the developmental progression of the entire spectrum of early hematopoietic progenitors and to suppress an erythroid specific program of gene expression in alternative cell lineages. Last, the data mechanistically link E2A, cell cycle regulators, and the maintenance of the HSC pool in a common pathway.

Original languageEnglish (US)
Pages (from-to)1930-1935
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number6
DOIs
StatePublished - Feb 10 2009

Keywords

  • E47
  • Lymphoid/myeloid versus erythroid/megakaryocyte development
  • Self-renewal

ASJC Scopus subject areas

  • General

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