GSBS Student Publications

Title

Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency

UMMS Affiliation

Graduate School of Biomedical Sciences; The Whitehead Institute for Biomedical Research; Department of Cell Biology

Date

4-22-2008

Document Type

Article

Medical Subject Headings

Animals; B-Lymphocytes; *Cell Differentiation; Cell Nucleus; Embryonic Stem Cells; Humans; Mice; Pluripotent Stem Cells; Transcription Factors

Disciplines

Life Sciences | Medicine and Health Sciences

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-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.

Rights and Permissions

Citation: Cell. 2008 Apr 18;133(2):250-64. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

Cell

PubMed ID

18423197