Constitutively active SMAD2/3 are broad-scope potentiators of transcription-factor-mediated cellular reprogramming

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Ruetz, Tyson Joelca
  • dc.contributor.author Pfisterer, Ulrichca
  • dc.contributor.author Di Stefano, Bruno, 1984-ca
  • dc.contributor.author Ashmore, Jamesca
  • dc.contributor.author Beniazza, Meryamca
  • dc.contributor.author Tian, Tian V.ca
  • dc.contributor.author Kaemena, Daniel F.ca
  • dc.contributor.author Tosti, Lucaca
  • dc.contributor.author Tan, Wenfangca
  • dc.contributor.author Manning, Jonathan R.ca
  • dc.contributor.author Chantzoura, Elenica
  • dc.contributor.author Ottosson, Daniella Rylanderca
  • dc.contributor.author Collombet, Samuelca
  • dc.contributor.author Johnsson, Anna E.ca
  • dc.contributor.author Cohen, Erezca
  • dc.contributor.author Yusa, Kosukeca
  • dc.contributor.author Linnarsson, Stenca
  • dc.contributor.author Graf, T. (Thomas)ca
  • dc.contributor.author Parmar, Malinca
  • dc.contributor.author Kaji, Keisukeca
  • dc.date.accessioned 2018-05-24T07:54:33Z
  • dc.date.available 2018-05-24T07:54:33Z
  • dc.date.issued 2017
  • dc.description.abstract Reprogramming of cellular identity using exogenous expression of transcription factors (TFs) is a powerful and exciting tool for tissue engineering, disease modeling, and regenerative medicine. However, generation of desired cell types using this approach is often plagued by inefficiency, slow conversion, and an inability to produce mature functional cells. Here, we show that expression of constitutively active SMAD2/3 significantly improves the efficiency of induced pluripotent stem cell (iPSC) generation by the Yamanaka factors. Mechanistically, SMAD3 interacts with reprogramming factors and co-activators and co-occupies OCT4 target loci during reprogramming. Unexpectedly, active SMAD2/3 also markedly enhances three other TF-mediated direct reprogramming conversions, from B cells to macrophages, myoblasts to adipocytes, and human fibroblasts to neurons, highlighting broad and general roles for SMAD2/3 as cell-reprogramming potentiators. Our results suggest that co-expression of active SMAD2/3 could enhance multiple types of TF-based cell identity conversion and therefore be a powerful tool for cellular engineering.
  • dc.description.sponsorship This work was supported by the ERC (grants ROADTOIPS 261075 to K.K. and BRAINCELL 261063 to S.L. and iN-Brain 309712 to M.P.), the BBSRC (project grant BB/L023474/1 to K.K.), the Anne Rowling Regenerative Neurology Clinic (K.K.), the Swedish Research Council (grant STARGET to S.L. and grants 521-2012-5624 and 521-2013-3347 to M.P.), and the Wellcome Trust (grant WT098051 to K.Y.). T.R., L.T., J.A., and D.F.K. are funded by a Darwin Trust scholarship, a CMVM scholarship, and Principal's Career Development scholarship from the University of Edinburgh, respectively. D.F.K. is supported by the BBSRC (EASTBIO doctoral training partnership). T.V.T. is supported by a Juan de la Cierva postdoctoral fellowship (MINECO, FJCI-2014-22946). B.D.S. was supported by an EMBO long-term fellowship (ALTF 1143-2015). K.K. is an MRC senior non-clinical fellow (MR/N008715/1). M.P. is a New York Stem Cell Foundation Robertson Investigator.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Ruetz T, Pfisterer U, Di Stefano B, Ashmore J, Beniazza M, Tian TV et al. Constitutively Active SMAD2/3 Are Broad-Scope Potentiators of Transcription-Factor-Mediated Cellular Reprogramming. Cell Stem Cell. 2017 Dec 7;21(6):791-805. DOI: 10.1016/j.stem.2017.10.013
  • dc.identifier.doi http://dx.doi.org/10.1016/j.stem.2017.10.013
  • dc.identifier.issn 1875-9777
  • dc.identifier.uri http://hdl.handle.net/10230/34718
  • dc.language.iso eng
  • dc.publisher Elsevierca
  • dc.relation.ispartof Cell Stem Cell. 2017 Dec 7;21(6):791-805
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/261075
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/261063
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/309712
  • dc.rights © 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Smad2
  • dc.subject.keyword Smad3
  • dc.subject.keyword Direct reprogramming
  • dc.subject.keyword iPSCs
  • dc.subject.keyword Induced neuron
  • dc.subject.keyword Reprogramming
  • dc.subject.keyword Transdifferentiation
  • dc.title Constitutively active SMAD2/3 are broad-scope potentiators of transcription-factor-mediated cellular reprogrammingca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Center for Genomic Regulation (CRG))
Articles (Departament de Medicina i Ciències de la Vida)
Documents OpenAIRE (Open Access Infrastructure for Research in Europe)