Logo do repositório
 
Publicação

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

dc.contributor.authorKubasova, Nadiya
dc.contributor.authorAlves-Pereira, Clara F.
dc.contributor.authorGupta, Saumya
dc.contributor.authorVinogradova, Svetlana
dc.contributor.authorGimelbrant, Alexander
dc.contributor.authorBarreto, Vasco M.
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionDCV - Departamento de Ciências da Vida
dc.contributor.institutionFaculdade de Ciências e Tecnologia (FCT)
dc.contributor.institutionUCIBIO - Applied Molecular Biosciences Unit
dc.contributor.pblFrontiers Media
dc.date.accessioned2022-09-05T22:30:48Z
dc.date.available2022-09-05T22:30:48Z
dc.date.issued2022-08-08
dc.descriptionFunding 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.
dc.description.abstractEvaluating 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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent4678981
dc.identifier.doi10.3389/fcell.2022.827774
dc.identifier.issn2296-634X
dc.identifier.otherPURE: 46368643
dc.identifier.otherPURE UUID: bed16c90-e308-44d4-8e7d-ce4f2c89ac19
dc.identifier.otherScopus: 85136528059
dc.identifier.otherPubMed: 36003148
dc.identifier.urihttp://hdl.handle.net/10362/143511
dc.identifier.urlhttps://www.scopus.com/pages/publications/85136528059
dc.language.isoeng
dc.peerreviewedyes
dc.subjectallele-specific expression
dc.subjectallelic imbalance (AI)
dc.subjectclonal analysis
dc.subjectepigenetics
dc.subjecthematopoietic stem cell (HSC)
dc.subjectrandom monoallelic expression (RME)
dc.subjectRNA-seq
dc.subjectX-chromosome inactivation (XCI)
dc.subjectDevelopmental Biology
dc.subjectCell Biology
dc.titleIn Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cellsen
dc.typejournal article
degois.publication.titleFrontiers in Cell and Developmental Biology
degois.publication.volume10
dspace.entity.typePublication
rcaap.rightsopenAccess

Ficheiros

Principais
A mostrar 1 - 1 de 1
A carregar...
Miniatura
Nome:
fcell_10_827774.pdf
Tamanho:
4.46 MB
Formato:
Adobe Portable Document Format