E proteins and the regulation of early lymphocyte development.
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.
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Renée F
RF
de Pooter
Barbara L
BL
Kee
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D051792:Basic Helix-Loop-Helix Proteins / Q000276:immunology*; D019070:Cell Lineage; D050990:GATA3 Transcription Factor / Q000276:immunology; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D006801:Humans; D054503:Lymphoid Progenitor Cells / Q000276:immunology; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology; D039902:Multipotent Stem Cells / Q000276:immunology*; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology*
D051792:Basic Helix-Loop-Helix Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C407909:TCF3 protein, human