Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1
Vivori, Claludia (The Francis Crick Institute)
Papasaikas, Panagiotis (Friedrich Miescher Institute for Biomedical Research)
Stadhouders, Ralph (Erasmus Medical Center. Departments of Pulmonary Medicine and Cell Biology)
Di Stefano, Bruno (Baylor College of Medicine (Houston, Estats Units d'Amèrica). Department of Molecular and Cellular Biology)
Ribó Rubio, Anna (Centre de Regulació Genòmica)
Berenguer Balaguer, Clara (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Generoso, Serena (Universitat Pompeu Fabra)
Mallol, Anna (Centre de Regulació Genòmica)
Sardina, José Luis (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Payer, Bernhard (Universitat Pompeu Fabra)
Graf, Thomas (Universitat Pompeu Fabra)
Valcárcel, Juan. (Institució Catalana de Recerca i Estudis Avançats)
Universitat Autònoma de Barcelona

Data:	2021
Resum:	Background: Somatic cell reprogramming is the process that allows differentiated cells to revert to a pluripotent state. In contrast to the extensively studied rewiring of epigenetic and transcriptional programs required for reprogramming, the dynamics of post-transcriptional changes and their associated regulatory mechanisms remain poorly understood. Here we study the dynamics of alternative splicing changes occurring during efficient reprogramming of mouse B cells into induced pluripotent stem (iPS) cells and compare them to those occurring during reprogramming of mouse embryonic fibroblasts. Results: We observe a significant overlap between alternative splicing changes detected in the two reprogramming systems, which are generally uncoupled from changes in transcriptional levels. Correlation between gene expression of potential regulators and specific clusters of alternative splicing changes enables the identification and subsequent validation of CPSF3 and hnRNP UL1 as facilitators, and TIA1 as repressor of mouse embryonic fibroblasts reprogramming. We further find that these RNA-binding proteins control partially overlapping programs of splicing regulation, involving genes relevant for developmental and morphogenetic processes. Conclusions: Our results reveal common programs of splicing regulation during reprogramming of different cell types and identify three novel regulators of this process and their targets.
Ajuts:	European Commission 670146 Ministerio de Economía y Competitividad SAF2012-37167 Agència de Gestió d'Ajuts Universitaris i de Recerca BFU201789308-P
Nota:	C.V. was recipient of an FPI-Severo Ochoa Fellowship from the Spanish Ministry of Economy and Competitiveness. Work in J.V. laboratory is supported by the European Research Council (ERC AdvG 670146), AGAUR, Spanish Ministry of Economy and Competitiveness (BFU 2017 89308-P) and the Centre of Excellence Severo Ochoa. Work in T.G.'s laboratory was supported by the European Research Council FP7/2007-2013 (ERC Synergy Grant 4D-Genome) the Ministerio de Educación y Ciencia (SAF.2012-37167) and AGAUR. We acknowledge support of the Spanish Ministry of Science and Innovation to the EMBL partnership and the CERCA Programme / Generalitat de Catalunya.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Genome biology, Vol. 22 Núm. 1 (december 2021) , p. 171, ISSN 1474-760X

DOI: 10.1186/s13059-021-02372-5
PMID: 34082786

30 p, 2.8 MB

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