Regulation of lymphoid versus myeloid fate 'choice' by the transcription factor Mef2c.
Despite advances in the identification of lymphoid-restricted progenitor cells, the transcription factors essential for their generation remain to be identified. Here we describe an unexpected function for the myeloid oncogene product Mef2c in lymphoid development. Mef2c deficiency was associated with profound defects in the production of B cells, T cells, natural killer cells and common lymphoid progenitor cells and an enhanced myeloid output. In multipotent progenitors, Mef2c was required for the proper expression of several key lymphoid regulators and restriction of the myeloid fate. Our studies also show that Mef2c was a critical transcriptional target of the transcription factor PU.1 during lymphopoiesis. Thus, Mef2c is a crucial component of the transcriptional network that regulates cell fate 'choice' in multipotent progenitors.
Stehling-Sun
Sandra
S
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Dade
Jessica
J
Nutt
Stephen L
SL
DeKoter
Rodney P
RP
Camargo
Fernando D
FD
D000818:Animals; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018380:Hematopoietic Stem Cell Transplantation; D054503:Lymphoid Progenitor Cells / Q000378:metabolism*; D038041:Lymphopoiesis; D064326:MEF2 Transcription Factors; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C578041:Mef2c protein, mouse