Journal
IMMUNOLOGICAL REVIEWS
Volume 238, Issue -, Pages 93-109Publisher
WILEY
DOI: 10.1111/j.1600-065X.2010.00957.x
Keywords
hematopoietic progenitor cells; lineage commitment; transcription factors; cell differentiation; gene regulation
Categories
Funding
- NIH [R01s CA099978, AI079213, AI078267]
- American Cancer Society
- Leukemia and Lymphoma Society
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Lymphopoiesis generates mature B, T, and NK lymphocytes from hematopoietic stem cells via a series of increasingly restricted developmental intermediates. The transcriptional networks that regulate these fate choices are composed of both common and lineage-specific components, which combine to create a cellular context that informs the developmental response to external signals. E proteins are an important factor during lymphopoiesis, and E2A in particular is required for normal T- and B-cell development. Although the other E proteins, HEB and E2-2, are expressed during lymphopoiesis and can compensate for some of E2A's activity, E2A proteins have non-redundant functions during early T-cell development and at multiple checkpoints throughout B lymphopoiesis. More recently, a role for E2A has been demonstrated in the generation of lymphoid-primed multipotent progenitors and shown to favor their specification toward lymphoid over myeloid lineages. This review summarizes both our current understanding of the wide-ranging functions of E proteins during the development of adaptive lymphocytes and the novel functions of E2A in orchestrating a lymphoid-biased cellular context in early multipotent progenitors.
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