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E proteins and the regulation of early lymphocyte development

Summary:  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.