Publicação
In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells
| dc.contributor.author | Kubasova, Nadiya | |
| dc.contributor.author | Alves-Pereira, Clara F. | |
| dc.contributor.author | Gupta, Saumya | |
| dc.contributor.author | Vinogradova, Svetlana | |
| dc.contributor.author | Gimelbrant, Alexander | |
| dc.contributor.author | Barreto, Vasco M. | |
| dc.contributor.institution | Centro de Estudos de Doenças Crónicas (CEDOC) | |
| dc.contributor.institution | NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) | |
| dc.contributor.institution | DCV - Departamento de Ciências da Vida | |
| dc.contributor.institution | Faculdade de Ciências e Tecnologia (FCT) | |
| dc.contributor.institution | UCIBIO - Applied Molecular Biosciences Unit | |
| dc.contributor.pbl | Frontiers Media | |
| dc.date.accessioned | 2022-09-05T22:30:48Z | |
| dc.date.available | 2022-09-05T22:30:48Z | |
| dc.date.issued | 2022-08-08 | |
| dc.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. | |
| dc.description.abstract | 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. | en |
| dc.description.version | publishersversion | |
| dc.description.version | published | |
| dc.format.extent | 4678981 | |
| dc.identifier.doi | 10.3389/fcell.2022.827774 | |
| dc.identifier.issn | 2296-634X | |
| dc.identifier.other | PURE: 46368643 | |
| dc.identifier.other | PURE UUID: bed16c90-e308-44d4-8e7d-ce4f2c89ac19 | |
| dc.identifier.other | Scopus: 85136528059 | |
| dc.identifier.other | PubMed: 36003148 | |
| dc.identifier.uri | http://hdl.handle.net/10362/143511 | |
| dc.identifier.url | https://www.scopus.com/pages/publications/85136528059 | |
| dc.language.iso | eng | |
| dc.peerreviewed | yes | |
| dc.subject | allele-specific expression | |
| dc.subject | allelic imbalance (AI) | |
| dc.subject | clonal analysis | |
| dc.subject | epigenetics | |
| dc.subject | hematopoietic stem cell (HSC) | |
| dc.subject | random monoallelic expression (RME) | |
| dc.subject | RNA-seq | |
| dc.subject | X-chromosome inactivation (XCI) | |
| dc.subject | Developmental Biology | |
| dc.subject | Cell Biology | |
| dc.title | In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells | en |
| dc.type | journal article | |
| degois.publication.title | Frontiers in Cell and Developmental Biology | |
| degois.publication.volume | 10 | |
| dspace.entity.type | Publication | |
| rcaap.rights | openAccess |
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