Direct Reprogramming of Terminally Differentiated Mature B Lymphocytes to Pluripotency

Jacob Hanna, Styliani Markoulaki, Patrick Schorderet, Bryce W. Carey, Caroline Beard, Marius Wernig, Menno P P. Creyghton, Eveline J. Steine, John P. Cassady, Ruth Foreman, Christopher J. Lengner, Jessica A A. Dausman, Rudolf Jaenisch*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

356 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)250-264
Number of pages15
JournalCell
Volume133
Issue number2
DOIs
StatePublished - Apr 18 2008

Keywords

  • CELLBIO
  • CELLIMMUNO
  • STEMCELL

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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