[HTML][HTML] Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency

J Hanna, S Markoulaki, P Schorderet, BW Carey… - cell, 2008 - cell.com
J Hanna, S Markoulaki, P Schorderet, BW Carey, C Beard, M Wernig, MP Creyghton…
cell, 2008cell.com
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 …
Summary
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-α (C/EBPα) 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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