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

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 hematop...

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Autores principales: Kubasova, Nadiya, Alves-Pereira, Clara F., Gupta, Saumya, Vinogradova, Svetlana, Gimelbrant, Alexander, Barreto, Vasco M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393635/
https://www.ncbi.nlm.nih.gov/pubmed/36003148
http://dx.doi.org/10.3389/fcell.2022.827774
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author Kubasova, Nadiya
Alves-Pereira, Clara F.
Gupta, Saumya
Vinogradova, Svetlana
Gimelbrant, Alexander
Barreto, Vasco M.
author_facet Kubasova, Nadiya
Alves-Pereira, Clara F.
Gupta, Saumya
Vinogradova, Svetlana
Gimelbrant, Alexander
Barreto, Vasco M.
author_sort Kubasova, Nadiya
collection PubMed
description 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.
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spelling pubmed-93936352022-08-23 In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells Kubasova, Nadiya Alves-Pereira, Clara F. Gupta, Saumya Vinogradova, Svetlana Gimelbrant, Alexander Barreto, Vasco M. Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2022-08-08 /pmc/articles/PMC9393635/ /pubmed/36003148 http://dx.doi.org/10.3389/fcell.2022.827774 Text en Copyright © 2022 Kubasova, Alves-Pereira, Gupta, Vinogradova, Gimelbrant and Barreto. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Kubasova, Nadiya
Alves-Pereira, Clara F.
Gupta, Saumya
Vinogradova, Svetlana
Gimelbrant, Alexander
Barreto, Vasco M.
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
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_short 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
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393635/
https://www.ncbi.nlm.nih.gov/pubmed/36003148
http://dx.doi.org/10.3389/fcell.2022.827774
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