In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells

Detalhes bibliográficos
Autor(a) principal: Kubasova, Nadiya
Data de Publicação: 2022
Outros Autores: Alves-Pereira, Clara F., Gupta, Saumya, Vinogradova, Svetlana, Gimelbrant, Alexander, Barreto, Vasco M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/143511
Resumo: Funding Information: This work has received funding from the FCT (Fundação para a Ciência e a Tecnologia) under grants PTDC/BEX-BCM/5900/2014 and IF/ 1823 01721/2014/CP1252/CT0005, and European Union’s Horizon 2020 research and innovation programme under grant agreement No. 752806. NK received a fellowship (PD/BD/114164/2016) from FCT. Publisher Copyright: Copyright © 2022 Kubasova, Alves-Pereira, Gupta, Vinogradova, Gimelbrant and Barreto.
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spelling In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cellsallele-specific expressionallelic imbalance (AI)clonal analysisepigeneticshematopoietic stem cell (HSC)random monoallelic expression (RME)RNA-seqX-chromosome inactivation (XCI)Developmental BiologyCell BiologyFunding Information: This work has received funding from the FCT (Fundação para a Ciência e a Tecnologia) under grants PTDC/BEX-BCM/5900/2014 and IF/ 1823 01721/2014/CP1252/CT0005, and European Union’s Horizon 2020 research and innovation programme under grant agreement No. 752806. NK received a fellowship (PD/BD/114164/2016) from FCT. Publisher Copyright: Copyright © 2022 Kubasova, Alves-Pereira, Gupta, Vinogradova, Gimelbrant and Barreto.Evaluating the epigenetic landscape in the stem cell compartment at the single-cell level is essential to assess the cells’ heterogeneity and predict their fate. Here, using a genome-wide transcriptomics approach in vivo, we evaluated the allelic expression imbalance in the progeny of single hematopoietic cells (HSCs) as a read-out of epigenetic marking. After 4 months of extensive proliferation and differentiation, we found that X-chromosome inactivation (XCI) is tightly maintained in all single-HSC derived hematopoietic cells. In contrast, the vast majority of the autosomal genes did not show clonal patterns of random monoallelic expression (RME). However, a persistent allele-specific autosomal transcription in HSCs and their progeny was found in a rare number of cases, none of which has been previously reported. These data show that: 1) XCI and RME in the autosomal chromosomes are driven by different mechanisms; 2) the previously reported high frequency of genes under RME in clones expanded in vitro (up to 15%) is not found in clones undergoing multiple differentiation steps in vivo; 3) prior to differentiation, HSCs have stable patterns of autosomal RME. We propose that most RME patterns in autosomal chromosomes are erased and established de novo during cell lineage differentiation.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)DCV - Departamento de Ciências da VidaFaculdade de Ciências e Tecnologia (FCT)RUNKubasova, NadiyaAlves-Pereira, Clara F.Gupta, SaumyaVinogradova, SvetlanaGimelbrant, AlexanderBarreto, Vasco M.2022-09-05T22:30:48Z2022-08-082022-08-08T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/143511eng2296-634XPURE: 46368643https://doi.org/10.3389/fcell.2022.827774info: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:RCAAP2024-03-11T05:21:53Zoai:run.unl.pt:10362/143511Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:50:58.895821Repositório 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 In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells
title In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells
spellingShingle In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells
Kubasova, Nadiya
allele-specific expression
allelic imbalance (AI)
clonal analysis
epigenetics
hematopoietic stem cell (HSC)
random monoallelic expression (RME)
RNA-seq
X-chromosome inactivation (XCI)
Developmental Biology
Cell Biology
title_short In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells
title_full In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells
title_fullStr In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells
title_full_unstemmed In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells
title_sort In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells
author Kubasova, Nadiya
author_facet Kubasova, Nadiya
Alves-Pereira, Clara F.
Gupta, Saumya
Vinogradova, Svetlana
Gimelbrant, Alexander
Barreto, Vasco M.
author_role author
author2 Alves-Pereira, Clara F.
Gupta, Saumya
Vinogradova, Svetlana
Gimelbrant, Alexander
Barreto, Vasco M.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
DCV - Departamento de Ciências da Vida
Faculdade de Ciências e Tecnologia (FCT)
RUN
dc.contributor.author.fl_str_mv Kubasova, Nadiya
Alves-Pereira, Clara F.
Gupta, Saumya
Vinogradova, Svetlana
Gimelbrant, Alexander
Barreto, Vasco M.
dc.subject.por.fl_str_mv allele-specific expression
allelic imbalance (AI)
clonal analysis
epigenetics
hematopoietic stem cell (HSC)
random monoallelic expression (RME)
RNA-seq
X-chromosome inactivation (XCI)
Developmental Biology
Cell Biology
topic allele-specific expression
allelic imbalance (AI)
clonal analysis
epigenetics
hematopoietic stem cell (HSC)
random monoallelic expression (RME)
RNA-seq
X-chromosome inactivation (XCI)
Developmental Biology
Cell Biology
description Funding Information: This work has received funding from the FCT (Fundação para a Ciência e a Tecnologia) under grants PTDC/BEX-BCM/5900/2014 and IF/ 1823 01721/2014/CP1252/CT0005, and European Union’s Horizon 2020 research and innovation programme under grant agreement No. 752806. NK received a fellowship (PD/BD/114164/2016) from FCT. Publisher Copyright: Copyright © 2022 Kubasova, Alves-Pereira, Gupta, Vinogradova, Gimelbrant and Barreto.
publishDate 2022
dc.date.none.fl_str_mv 2022-09-05T22:30:48Z
2022-08-08
2022-08-08T00:00:00Z
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/10362/143511
url http://hdl.handle.net/10362/143511
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2296-634X
PURE: 46368643
https://doi.org/10.3389/fcell.2022.827774
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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