PU.1 determines the self-renewal capacity of erythroid progenitor cells.
PU.1 is a hematopoietic-specific transcriptional activator that is absolutely required for the differentiation of B lymphocytes and myeloid-lineage cells. Although PU.1 is also expressed by early erythroid progenitor cells, its role in erythropoiesis, if any, is unknown. To investigate the relevance of PU.1 in erythropoiesis, we produced a line of PU.1-deficient mice carrying a green fluorescent protein reporter at this locus. We report here that PU.1 is tightly regulated during differentiation-it is expressed at low levels in erythroid progenitor cells and down-regulated upon terminal differentiation. Strikingly, PU.1-deficient fetal erythroid progenitors lose their self-renewal capacity and undergo proliferation arrest, premature differentiation, and apoptosis. In adult mice lacking one PU.1 allele, similar defects are detected following stress-induced erythropoiesis. These studies identify PU.1 as a novel and critical regulator of erythropoiesis and highlight the versatility of this transcription factor in promoting or preventing differentiation depending on the hematopoietic lineage.
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Jonathan
J
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CEDEX, France.
Dierich
Andrée
A
Bronn
Corinne
C
Kastner
Philippe
P
Chan
Susan
S
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D004900:Erythroblasts / Q000166:cytology; D015672:Erythroid Precursor Cells / Q000166:cytology*; D004920:Erythropoiesis; D005333:Fetus; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D000099232:Proto-Oncogene Protein Spi-1
D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1