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Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation

2022Artigo científico Acesso aberto
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dc.contributor.authorArez, Maria
dc.contributor.authorEckersley-Maslin, Melanie
dc.contributor.authorKlobuar, Tajda
dc.contributor.authorvon Gilsa Lopes, João
dc.contributor.authorKrueger, Felix
dc.contributor.authorMupo, Annalisa
dc.contributor.authorRaposo, Ana Cláudia
dc.contributor.authorOxley, David
dc.contributor.authorMancino, Samantha
dc.contributor.authorGendrel, Anne-Valerie
dc.contributor.authorJesus, Bruno Bernardes De
dc.contributor.authorda Rocha, Simão T.
dc.date.accessioned2022-09-19T15:14:17Z
dc.date.available2022-09-19T15:14:17Z
dc.date.issued2022
dc.description© The Author(s) 2022 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.pt_PT
dc.description.abstractReprogramming of somatic cells into induced Pluripotent Stem Cells (iPSCs) is a major leap towards personalised approaches to disease modelling and cell-replacement therapies. However, we still lack the ability to fully control the epigenetic status of iPSCs, which is a major hurdle for their downstream applications. Epigenetic fidelity can be tracked by genomic imprinting, a phenomenon dependent on DNA methylation, which is frequently perturbed in iPSCs by yet unknown reasons. To try to understand the causes underlying these defects, we conducted a thorough imprinting analysis using IMPLICON, a high-throughput method measuring DNA methylation levels, in multiple female and male murine iPSC lines generated under different experimental conditions. Our results show that imprinting defects are remarkably common in iPSCs, but their nature depends on the sex of donor cells and their response to culture conditions. Imprints in female iPSCs resist the initial genome-wide DNA demethylation wave during reprogramming, but ultimately cells accumulate hypomethylation defects irrespective of culture medium formulations. In contrast, imprinting defects on male iPSCs depends on the experimental conditions and arise during reprogramming, being mitigated by the addition of vitamin C (VitC). Our findings are fundamental to further optimise reprogramming strategies and generate iPSCs with a stable epigenome.pt_PT
dc.description.sponsorshipWork in S.T.d.R.’s team was supported by Fundação para a Ciência e Tecnologia (FCT) Ministério da Ciência, Tecnologia e Ensino Superior (MCTES), Portugal [IC&DT projects PTDC/BEX-BCM/2612/2014 and PTDC/BIA-MOL/29320/2017 as well as projects UIDB/04565/2020 and UIDP/04565/2020 of the Research Unit Institute from Bioengineering and Biosciences – iBB and LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy – i4HB]; S.T.d.R. and A.-V.G. are supported by assistant research contracts from FCT/MCTES (CEECIND/01234/2017 and CEECIND/02085/2018, respectively); M.A and A.C.R. are supported, respectively, by SFRH/BD/151251/2021 and SFRH/BD/137099/2018 PhD fellowships from FCT/MCTES. J.V.G.L is supported by COVID/BD/152624/2022 from FCT/MCTES. MAE-M was supported by a BBSRC Discovery Fellowship (BB/T009713/1) and is now supported by a Snow Medical Fellowship. F.K. is supported by the Babraham Institute Strategic Core Funding and A.M. by BBSRC BBS/E/B/000C0421. B.B.J. work was funded by Fundação para a Ciência e Tecnologia (FCT), and FEDER, LISBOA-01-0145-FEDER-028534, project co-funded by FEDER, through POR Lisboa 2020—Programa Operacional Regional de Lisboa. T.K. is supported by Janko Jamnik Doctoral Scholarship from National Institute of Chemistry.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNat Commun. 2022 Sep 16;13(1):5432pt_PT
dc.identifier.doi10.1038/s41467-022-33013-5pt_PT
dc.identifier.eissn2041-1723
dc.identifier.urihttp://hdl.handle.net/10451/54505
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relationSFRH/BD/151251/2021pt_PT
dc.relationInstitute for Bioengineering and Biosciences
dc.relationInstitute for Bioengineering and Biosciences
dc.relationNot Available
dc.relationNot Available
dc.relationFunctional dissection of the XIST non-coding RNA in X-chromosome inactivation in human ESCs
dc.relationThe role of Cerl2 in cardiomyocyte differentiantion and heart regeneration
dc.relation.publisherversionhttps://www.nature.com/ncomms/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleImprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberPTDC/BEX-BCM/2612/2014
oaire.awardNumberPTDC/BIA-MOL/29320/2017
oaire.awardNumberUIDB/04565/2020
oaire.awardNumberUIDP/04565/2020
oaire.awardNumberCEECIND/01234/2017/CP1396/CT0002
oaire.awardNumberCEECIND/02085/2018/CP1543/CT0008
oaire.awardNumberSFRH/BD/137099/2018
oaire.awardNumberCOVID/BD/152624/2022
oaire.awardTitleInstitute for Bioengineering and Biosciences
oaire.awardTitleInstitute for Bioengineering and Biosciences
oaire.awardTitleNot Available
oaire.awardTitleNot Available
oaire.awardTitleFunctional dissection of the XIST non-coding RNA in X-chromosome inactivation in human ESCs
oaire.awardTitleThe role of Cerl2 in cardiomyocyte differentiantion and heart regeneration
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBEX-BCM%2F2612%2F2014/PT
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oaire.awardURIinfo:eu-repo/grantAgreement/FCT/CEEC IND 2018/CEECIND%2F02085%2F2018%2FCP1543%2FCT0008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F137099%2F2018/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/COVID%2FBD%2F152624%2F2022/PT
oaire.citation.issue1pt_PT
oaire.citation.titleNature Communicationspt_PT
oaire.citation.volume13pt_PT
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