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

• DOI: 10.1073/pnas.0808866106
• Publication Date: 2009-01-31T01:55:31Z
• Authors: Craig L. Semerad; Elinore M. Mercer; Matthew A. Inlay; Irving L. Weissman; Cornelis Murre
• Keywords: Hematopoietic stem cell

Hematopoiesis is a tightly controlled process maintained by small pool of hematopoietic stem cells (HSCs). Here, we demonstrate that the LT-HSC, MPP, premegakaryocytic/erythroid, Pre CFU-E, GM, MkP, and granulocyte-macrophage compartments were all significantly reduced in E2A-deficient bone marrow. Despite severe depletion erythroid progenitors, erythrocyte megakaryocyte equivalent marrow as compared with wild-type mice. HSCs also failed to efficiently maintain HSC on serial transplantation, E2A proteins regulate cell cycle progression regulating expression p21 Cip1 , p27 Kip1 thrombopoietin receptor, known regulators self-renewal activity. Based these observations, propose promote developmental entire spectrum early progenitors suppress an specific program gene alternative lineages. Last, data mechanistically link E2A, regulators, maintenance common pathway.