In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells
Autor(a) principal: | |
---|---|
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/10362/143511 |
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. |
id |
RCAP_ce7861e24901c6606a2c7d7bb4a6620a |
---|---|
oai_identifier_str |
oai:run.unl.pt:10362/143511 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
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 |
|
_version_ |
1799138104693489664 |