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
DOI of Published Version
10.1016/j.cell.2008.03.028
Related Resources
Journal Title
Cell
PubMed ID
18423197
Repository Citation
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.
https://escholarship.umassmed.edu/gsbs_sp/1485