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In vivo clonal analysis reveals random monoallelic expression in lymphocytes that traces back to hematopoietic stem cells

datacite.subject.fosCiências Médicas
datacite.subject.sdg03:Saúde de Qualidade
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.date.accessioned2025-11-17T12:17:34Z
dc.date.available2025-11-17T12:17:34Z
dc.date.issued2022-08
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.eng
dc.identifier.citationKubasova N, Alves-Pereira CF, Gupta S, Vinogradova S, Gimelbrant A and Barreto VM (2022) In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells. Front. Cell Dev. Biol. 10:827774. doi: 10.3389/fcell.2022.827774
dc.identifier.doi10.3389/fcell.2022.827774
dc.identifier.issn2296-634X
dc.identifier.urihttp://hdl.handle.net/10400.26/59812
dc.language.isoeng
dc.peerreviewedyes
dc.publisherFrontiers Media
dc.relation.hasversionhttps://doi.org/10.3389/fcell.2022.827774
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectallele-specific expression
dc.subjectrandom monoallelic expression (RME)
dc.subjectallelic imbalance (AI)
dc.subjectepigenetics
dc.subjectclonal analysis
dc.subjecthematopoietic stem cell (HSC)
dc.subjectX-chromosome inactivation (XCI)
dc.subjectRNA-seq
dc.titleIn vivo clonal analysis reveals random monoallelic expression in lymphocytes that traces back to hematopoietic stem cellseng
dc.typecontribution to journal
dspace.entity.typePublication
oaire.citation.startPage827774
oaire.citation.titleFrontiers in Cell and Developmental Biology
oaire.citation.volume10
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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