Regulation of B lymphocyte and macrophage development by graded expression of PU.1.
The ets family transcription factor PU.1 is required for the development of multiple lineages of the immune system. Using retroviral transduction of PU.1 complementary DNA into mutant hematopoietic progenitors, we demonstrate that differing concentrations of the protein regulate the development of B lymphocytes as compared with macrophages. A low concentration of PU. 1 protein induces the B cell fate, whereas a high concentration promotes macrophage differentiation and blocks B cell development. Conversely, a transcriptionally weakened mutant protein preferentially induces B cell generation. Our results suggest that graded expression of a transcription factor can be used to specify distinct cell fates in the hematopoietic system.
DeKoter
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Howard Hughes Medical Institute and Department of Molecular Genetics and Cell Biology, The University of Chicago, 5841 South Maryland Avenue, MC1028, Chicago, IL 60637, USA.
Singh
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D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D002478:Cells, Cultured; D018920:Coculture Techniques; D018076:DNA, Complementary; D015870:Gene Expression; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D051379:Mice; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D014161:Transduction, Genetic; D000099232:Proto-Oncogene Protein Spi-1
D018076:DNA, Complementary; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1