西亚试剂：Direct Reprogramming of Terminally Differentiated Mature B

Direct Reprogramming of Terminally Differentiated Mature B Lymphocytes to Pluripotency
Jacob Hanna,1 Styliani Markoulaki,1 Patrick Schorderet,1 Bryce W. Carey,1,2 Caroline Beard,1 Marius Wernig,1 Menno P. Creyghton,1 Eveline J. Steine,1 John P. Cassady,1,2 Ruth Foreman,1,2 Christopher J. Lengner,1 Jessica A. Dausman,1 and Rudolf Jaenisch1,2,

1 The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
2 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA

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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