5-Azacytidine induction of stable mesodermal stem cell lineages from 10T1/2 cells: evidence for regulatory genes controlling determination.
5-Azacytidine converts the mouse embryonic cell line C3H 10T1/2 into differentiated chondrocytes, adipocytes, and skeletal muscle. Clonal and 2D protein gel analyses demonstrate that 5-azacytidine converts 10T1/2 cells into three stably determined, but undifferentiated, stem cell lineages which can differentiate into myofibers, chondrocytes, and adipocytes. Conversion of 10T1/2 cells is accompanied by specific changes in protein synthetic patterns unique for each cell lineage. We propose that 5-azacytidine converts 10T1/2 cells by hypomethylation of "determination" regulatory loci which establish lineages of stem cells with a restricted potential to differentiate into muscle, cartilage, or fat cells. Our results suggest that these three lineages are specified by separate regulatory loci and that as few as 1-3 hypomethylation events per cell are sufficient to activate the hypothesized muscle regulatory locus. Conversion of 10T1/2 cells by 5-azacytidine provides a model for studying regulatory genes involved in cell lineage determination.
D000273:Adipose Tissue / Q000196:embryology / Q000378:metabolism; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D002356:Cartilage / Q000196:embryology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D004622:Embryo, Mammalian; D005809:Genes, Regulator; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009132:Muscles / Q000196:embryology / Q000378:metabolism
D003598:Cytoskeletal Proteins; D001374:Azacitidine