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Immunity. 2004 Mar;20(3):349-60.

Long-term cultured E2A-deficient hematopoietic progenitor cells are pluripotent.

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Division of Biological Sciences, 0377 University of California, San Diego, La Jolla, CA 92093, USA.


E2A proteins are essential for the development of B cells beyond the progenitor cell stage. Here we have isolated E2A-deficient bone marrow-derived cells that have the ability to grow long-term in vitro and coexpress, at low levels, regulators of different hematopoietic cell lineages. When transferred into lethally irradiated hosts, E2A-deficient hematopoietic progenitor cells reconstitute the T, NK, myeloid, dendritic, and erythroid lineages but fail to develop into mature B lineage cells. Enforced expression of E47 in E2A-deficient hematopoietic progenitor cells directly activates the transcription of a subset of B lineage-specific genes, including lambda5, mb-1, and Pax5. In contrast, E47 inhibits the expression of regulators of other hematopoietic lineages, including TCF-1 and GATA-1. These observations indicate that E2A-deficient hematopoietic progenitor cells remain pluripotent after long-term culture in vitro and that E2A proteins play a critical role in B cell commitment.

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