An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming

Mathieu Gabut, Payman Samavarchi-Tehrani, Xinchen Wang, Valentina Slobodeniuc, Dave O'Hanlon, Hoon Ki Sung, Manuel Alvarez, Shaheynoor Talukder, Qun Pan, Esteban O. Mazzoni, Stephane Nedelec, Hynek Wichterle, Knut Woltjen, Timothy R. Hughes, Peter W. Zandstra, Andras Nagy, Jeffrey L. Wrana, Benjamin J. Blencowe

Research output: Contribution to journalArticle

Abstract

Alternative splicing (AS) is a key process underlying the expansion of proteomic diversity and the regulation of gene expression. Here, we identify an evolutionarily conserved embryonic stem cell (ESC)-specific AS event that changes the DNA-binding preference of the forkhead family transcription factor FOXP1. We show that the ESC-specific isoform of FOXP1 stimulates the expression of transcription factor genes required for pluripotency, including OCT4, NANOG, NR5A2, and GDF3, while concomitantly repressing genes required for ESC differentiation. This isoform also promotes the maintenance of ESC pluripotency and contributes to efficient reprogramming of somatic cells into induced pluripotent stem cells. These results reveal a pivotal role for an AS event in the regulation of pluripotency through the control of critical ESC-specific transcriptional programs.

Original languageEnglish (US)
Pages (from-to)132-146
Number of pages15
JournalCell
Volume147
Issue number1
DOIs
StatePublished - Sep 30 2011

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Alternative Splicing
Embryonic Stem Cells
Stem cells
Switches
Protein Isoforms
Forkhead Transcription Factors
Transcription Factors
Induced Pluripotent Stem Cells
Genes
Gene Expression Regulation
Proteomics
Cell Differentiation
Gene expression
Maintenance
Cellular Reprogramming
DNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Gabut, M., Samavarchi-Tehrani, P., Wang, X., Slobodeniuc, V., O'Hanlon, D., Sung, H. K., ... Blencowe, B. J. (2011). An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming. Cell, 147(1), 132-146. https://doi.org/10.1016/j.cell.2011.08.023

An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming. / Gabut, Mathieu; Samavarchi-Tehrani, Payman; Wang, Xinchen; Slobodeniuc, Valentina; O'Hanlon, Dave; Sung, Hoon Ki; Alvarez, Manuel; Talukder, Shaheynoor; Pan, Qun; Mazzoni, Esteban O.; Nedelec, Stephane; Wichterle, Hynek; Woltjen, Knut; Hughes, Timothy R.; Zandstra, Peter W.; Nagy, Andras; Wrana, Jeffrey L.; Blencowe, Benjamin J.

In: Cell, Vol. 147, No. 1, 30.09.2011, p. 132-146.

Research output: Contribution to journalArticle

Gabut, M, Samavarchi-Tehrani, P, Wang, X, Slobodeniuc, V, O'Hanlon, D, Sung, HK, Alvarez, M, Talukder, S, Pan, Q, Mazzoni, EO, Nedelec, S, Wichterle, H, Woltjen, K, Hughes, TR, Zandstra, PW, Nagy, A, Wrana, JL & Blencowe, BJ 2011, 'An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming', Cell, vol. 147, no. 1, pp. 132-146. https://doi.org/10.1016/j.cell.2011.08.023
Gabut M, Samavarchi-Tehrani P, Wang X, Slobodeniuc V, O'Hanlon D, Sung HK et al. An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming. Cell. 2011 Sep 30;147(1):132-146. https://doi.org/10.1016/j.cell.2011.08.023
Gabut, Mathieu ; Samavarchi-Tehrani, Payman ; Wang, Xinchen ; Slobodeniuc, Valentina ; O'Hanlon, Dave ; Sung, Hoon Ki ; Alvarez, Manuel ; Talukder, Shaheynoor ; Pan, Qun ; Mazzoni, Esteban O. ; Nedelec, Stephane ; Wichterle, Hynek ; Woltjen, Knut ; Hughes, Timothy R. ; Zandstra, Peter W. ; Nagy, Andras ; Wrana, Jeffrey L. ; Blencowe, Benjamin J. / An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming. In: Cell. 2011 ; Vol. 147, No. 1. pp. 132-146.
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