Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency
Graduate School of Biomedical Sciences; The Whitehead Institute for Biomedical Research; Department of Cell Biology
Medical Subject Headings
Animals; B-Lymphocytes; *Cell Differentiation; Cell Nucleus; Embryonic Stem Cells; Humans; Mice; Pluripotent Stem Cells; Transcription Factors
Life Sciences | Medicine and Health Sciences
Pluripotent cells can be derived from fibroblasts by ectopic expression of defined transcription factors. A fundamental unresolved question is whether terminally differentiated cells can be reprogrammed to pluripotency. We utilized transgenic and inducible expression of four transcription factors (Oct4, Sox2, Klf4, and c-Myc) to reprogram mouse B lymphocytes. These factors were sufficient to convert nonterminally differentiated B cells to a pluripotent state. However, reprogramming of mature B cells required additional interruption with the transcriptional state maintaining B cell identity by either ectopic expression of the myeloid transcription factor CCAAT/enhancer-binding-protein-alpha (C/EBPalpha) or specific knockdown of the B cell transcription factor Pax5. Multiple iPS lines were clonally derived from both nonfully and fully differentiated B lymphocytes, which gave rise to adult chimeras with germline contribution, and to late-term embryos when injected into tetraploid blastocysts. Our study provides definite proof for the direct nuclear reprogramming of terminally differentiated adult cells to pluripotency.
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Citation: Cell. 2008 Apr 18;133(2):250-64. Link to article on publisher's site
Hanna, Jacob; Markoulaki, Styliani; Schorderet, Patrick; Carey, Bryce W.; Beard, Caroline F.; Wernig, Marius; Creyghton, Menno P.; Steine, Eveline J.; Cassady, John P.; Foreman, Ruth K.; Lengner, Christopher Joachim; Dausman, Jessica A.; and Jaenisch, Rudolf, "Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency" (2008). GSBS Student Publications. 1485.