Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1

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 assoc...

Descripción completa

Detalles Bibliográficos
Autores: Vivori, Claudia, 1989-, Papasaikas, Panagiotis, Stadhouders, Ralph, Di Stefano, Bruno, 1984-, Ribó Rubio, Anna, Berenguer Balaguer, Clara, Generoso, Serena Francesca, 1988-, Mallol, Anna, Sardina, Jose Luis, Payer, Bernhard, Graf, T. (Thomas), Valcárcel, J. (Juan)
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/49031
Acceso en línea:http://hdl.handle.net/10230/49031
http://dx.doi.org/10.1186/s13059-021-02372-5
Access Level:acceso abierto
Palabra clave:Alternative splicing
CPSF3
Pluripotency
Somatic cell reprogramming
TIA1
hnRNP UL1
id ES_49730067309a30fc6d9d5c1600cf4e8e
oai_identifier_str oai:recercat.cat:10230/49031
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1
title Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1
spellingShingle Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1
Vivori, Claudia, 1989-
Alternative splicing
CPSF3
Pluripotency
Somatic cell reprogramming
TIA1
hnRNP UL1
title_short Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1
title_full Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1
title_fullStr Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1
title_full_unstemmed Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1
title_sort Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1
dc.creator.none.fl_str_mv Vivori, Claudia, 1989-
Papasaikas, Panagiotis
Stadhouders, Ralph
Di Stefano, Bruno, 1984-
Ribó Rubio, Anna
Berenguer Balaguer, Clara
Generoso, Serena Francesca, 1988-
Mallol, Anna
Sardina, Jose Luis
Payer, Bernhard
Graf, T. (Thomas)
Valcárcel, J. (Juan)
author Vivori, Claudia, 1989-
author_facet Vivori, Claudia, 1989-
Papasaikas, Panagiotis
Stadhouders, Ralph
Di Stefano, Bruno, 1984-
Ribó Rubio, Anna
Berenguer Balaguer, Clara
Generoso, Serena Francesca, 1988-
Mallol, Anna
Sardina, Jose Luis
Payer, Bernhard
Graf, T. (Thomas)
Valcárcel, J. (Juan)
author_role author
author2 Papasaikas, Panagiotis
Stadhouders, Ralph
Di Stefano, Bruno, 1984-
Ribó Rubio, Anna
Berenguer Balaguer, Clara
Generoso, Serena Francesca, 1988-
Mallol, Anna
Sardina, Jose Luis
Payer, Bernhard
Graf, T. (Thomas)
Valcárcel, J. (Juan)
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alternative splicing
CPSF3
Pluripotency
Somatic cell reprogramming
TIA1
hnRNP UL1
topic Alternative splicing
CPSF3
Pluripotency
Somatic cell reprogramming
TIA1
hnRNP UL1
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/49031
http://dx.doi.org/10.1186/s13059-021-02372-5
url http://hdl.handle.net/10230/49031
http://dx.doi.org/10.1186/s13059-021-02372-5
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Genome Biol. 2021;22(1):171
info:eu-repo/grantAgreement/EC/H2020/670146
info:eu-repo/grantAgreement/ES/2PE/BFU2017-89308-P
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869407424994082816
spelling Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1Vivori, Claudia, 1989-Papasaikas, PanagiotisStadhouders, RalphDi Stefano, Bruno, 1984-Ribó Rubio, AnnaBerenguer Balaguer, ClaraGeneroso, Serena Francesca, 1988-Mallol, AnnaSardina, Jose LuisPayer, BernhardGraf, T. (Thomas)Valcárcel, J. (Juan)Alternative splicingCPSF3PluripotencySomatic cell reprogrammingTIA1hnRNP UL1Background: 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.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.BioMed Central202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/49031http://dx.doi.org/10.1186/s13059-021-02372-5reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésGenome Biol. 2021;22(1):171info:eu-repo/grantAgreement/EC/H2020/670146info:eu-repo/grantAgreement/ES/2PE/BFU2017-89308-P© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/490312026-05-29T05:05:01Z
score 15,198674