Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/144427 |
Resumo: | Funding Information: We would like to thank Sérgio de Almeida, Miguel Casanova and Inês Milagre for critical reading of the manuscript, and the members of the S.T.d.R.’s team for helpful discussions. We also thank Tânia Carvalho and Pedro Ruivo for their help in histological analysis; Judith Webster at Babraham Institute for LC-MS measurements; Bethan Hussey at Sanger Sequencing and Kristina Tabbada at Babraham Institute for assistance with high-throughput sequencing; and the Bioimaging unit as well as Andreia Santos, Rute Gonçalves and Mariana Fernandes of the Flow Cytometry Facility of Instituto de Medicina Molecular João Lobo Antunes for their services and assistance. Work 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. Funding Information: We would like to thank Sérgio de Almeida, Miguel Casanova and Inês Milagre for critical reading of the manuscript, and the members of the S.T.d.R.’s team for helpful discussions. We also thank Tânia Carvalho and Pedro Ruivo for their help in histological analysis; Judith Webster at Babraham Institute for LC-MS measurements; Bethan Hussey at Sanger Sequencing and Kristina Tabbada at Babraham Institute for assistance with high-throughput sequencing; and the Bioimaging unit as well as Andreia Santos, Rute Gonçalves and Mariana Fernandes of the Flow Cytometry Facility of Instituto de Medicina Molecular João Lobo Antunes for their services and assistance. Work 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. Publisher Copyright: © 2022, The Author(s). |
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Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulationChemistry(all)Biochemistry, Genetics and Molecular Biology(all)GeneralPhysics and Astronomy(all)Funding Information: We would like to thank Sérgio de Almeida, Miguel Casanova and Inês Milagre for critical reading of the manuscript, and the members of the S.T.d.R.’s team for helpful discussions. We also thank Tânia Carvalho and Pedro Ruivo for their help in histological analysis; Judith Webster at Babraham Institute for LC-MS measurements; Bethan Hussey at Sanger Sequencing and Kristina Tabbada at Babraham Institute for assistance with high-throughput sequencing; and the Bioimaging unit as well as Andreia Santos, Rute Gonçalves and Mariana Fernandes of the Flow Cytometry Facility of Instituto de Medicina Molecular João Lobo Antunes for their services and assistance. Work 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. Funding Information: We would like to thank Sérgio de Almeida, Miguel Casanova and Inês Milagre for critical reading of the manuscript, and the members of the S.T.d.R.’s team for helpful discussions. We also thank Tânia Carvalho and Pedro Ruivo for their help in histological analysis; Judith Webster at Babraham Institute for LC-MS measurements; Bethan Hussey at Sanger Sequencing and Kristina Tabbada at Babraham Institute for assistance with high-throughput sequencing; and the Bioimaging unit as well as Andreia Santos, Rute Gonçalves and Mariana Fernandes of the Flow Cytometry Facility of Instituto de Medicina Molecular João Lobo Antunes for their services and assistance. Work 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. Publisher Copyright: © 2022, The Author(s).Reprogramming 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.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNArez, MariaEckersley-Maslin, MelanieKlobučar, Tajdavon Gilsa Lopes, JoãoKrueger, FelixMupo, AnnalisaRaposo, Ana CláudiaOxley, DavidMancino, SamanthaGendrel, Anne ValerieBernardes de Jesus, Brunoda Rocha, Simão Teixeira2022-09-30T22:54:47Z2022-122022-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/144427eng2041-1723PURE: 46824311https://doi.org/10.1038/s41467-022-33013-5info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:24:06Zoai:run.unl.pt:10362/144427Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:51:33.168184Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation |
title |
Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation |
spellingShingle |
Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation Arez, Maria Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) General Physics and Astronomy(all) |
title_short |
Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation |
title_full |
Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation |
title_fullStr |
Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation |
title_full_unstemmed |
Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation |
title_sort |
Imprinting fidelity in mouse iPSCs depends on sex of donor cell and medium formulation |
author |
Arez, Maria |
author_facet |
Arez, Maria Eckersley-Maslin, Melanie Klobučar, Tajda von Gilsa Lopes, João Krueger, Felix Mupo, Annalisa Raposo, Ana Cláudia Oxley, David Mancino, Samantha Gendrel, Anne Valerie Bernardes de Jesus, Bruno da Rocha, Simão Teixeira |
author_role |
author |
author2 |
Eckersley-Maslin, Melanie Klobučar, Tajda von Gilsa Lopes, João Krueger, Felix Mupo, Annalisa Raposo, Ana Cláudia Oxley, David Mancino, Samantha Gendrel, Anne Valerie Bernardes de Jesus, Bruno da Rocha, Simão Teixeira |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) RUN |
dc.contributor.author.fl_str_mv |
Arez, Maria Eckersley-Maslin, Melanie Klobučar, Tajda von Gilsa Lopes, João Krueger, Felix Mupo, Annalisa Raposo, Ana Cláudia Oxley, David Mancino, Samantha Gendrel, Anne Valerie Bernardes de Jesus, Bruno da Rocha, Simão Teixeira |
dc.subject.por.fl_str_mv |
Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) General Physics and Astronomy(all) |
topic |
Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) General Physics and Astronomy(all) |
description |
Funding Information: We would like to thank Sérgio de Almeida, Miguel Casanova and Inês Milagre for critical reading of the manuscript, and the members of the S.T.d.R.’s team for helpful discussions. We also thank Tânia Carvalho and Pedro Ruivo for their help in histological analysis; Judith Webster at Babraham Institute for LC-MS measurements; Bethan Hussey at Sanger Sequencing and Kristina Tabbada at Babraham Institute for assistance with high-throughput sequencing; and the Bioimaging unit as well as Andreia Santos, Rute Gonçalves and Mariana Fernandes of the Flow Cytometry Facility of Instituto de Medicina Molecular João Lobo Antunes for their services and assistance. Work 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. Funding Information: We would like to thank Sérgio de Almeida, Miguel Casanova and Inês Milagre for critical reading of the manuscript, and the members of the S.T.d.R.’s team for helpful discussions. We also thank Tânia Carvalho and Pedro Ruivo for their help in histological analysis; Judith Webster at Babraham Institute for LC-MS measurements; Bethan Hussey at Sanger Sequencing and Kristina Tabbada at Babraham Institute for assistance with high-throughput sequencing; and the Bioimaging unit as well as Andreia Santos, Rute Gonçalves and Mariana Fernandes of the Flow Cytometry Facility of Instituto de Medicina Molecular João Lobo Antunes for their services and assistance. Work 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. Publisher Copyright: © 2022, The Author(s). |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-09-30T22:54:47Z 2022-12 2022-12-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/144427 |
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http://hdl.handle.net/10362/144427 |
dc.language.iso.fl_str_mv |
eng |
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eng |
dc.relation.none.fl_str_mv |
2041-1723 PURE: 46824311 https://doi.org/10.1038/s41467-022-33013-5 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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