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

doi:10.1016/j.cell.2011.08.023

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

Biology and Genomics

Research output: Contribution to journal › Article

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 language	English (US)
Pages (from-to)	132-146
Number of pages	15
Journal	Cell
Volume	147
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2011.08.023
State	Published - Sep 30 2011

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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Gabut, M., Samavarchi-Tehrani, P., Wang, X., Slobodeniuc, V., O'Hanlon, D., Sung, H. K., Alvarez, M., Talukder, S., Pan, Q., Mazzoni, E. O., Nedelec, S., Wichterle, H., Woltjen, K., Hughes, T. R., Zandstra, P. W., Nagy, A., Wrana, J. L., & 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 journal › Article

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, 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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AU - Mazzoni, Esteban O.

AU - Nedelec, Stephane

AU - Wichterle, Hynek

AU - Woltjen, Knut

AU - Hughes, Timothy R.

AU - Zandstra, Peter W.

AU - Nagy, Andras

AU - Wrana, Jeffrey L.

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