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Global genome decompaction leads to stochastic activation of gene expression as a first step toward fate commitment in human hematopoietic cells

When human cord blood–derived CD34+ cells are induced to differentiate, they undergo rapid and dynamic morphological and molecular transformations that are critical for fate commitment. In particular, the cells pass through a transitory phase known as “multilineage-primed” state. These cells are cha...

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Autores principales: Parmentier, Romuald, Racine, Laëtitia, Moussy, Alice, Chantalat, Sophie, Sudharshan, Ravi, Papili Gao, Nan, Stockholm, Daniel, Corre, Guillaume, Fourel, Geneviève, Deleuze, Jean-François, Gunawan, Rudiyanto, Paldi, Andras
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604949/
https://www.ncbi.nlm.nih.gov/pubmed/36288293
http://dx.doi.org/10.1371/journal.pbio.3001849
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author Parmentier, Romuald
Racine, Laëtitia
Moussy, Alice
Chantalat, Sophie
Sudharshan, Ravi
Papili Gao, Nan
Stockholm, Daniel
Corre, Guillaume
Fourel, Geneviève
Deleuze, Jean-François
Gunawan, Rudiyanto
Paldi, Andras
author_facet Parmentier, Romuald
Racine, Laëtitia
Moussy, Alice
Chantalat, Sophie
Sudharshan, Ravi
Papili Gao, Nan
Stockholm, Daniel
Corre, Guillaume
Fourel, Geneviève
Deleuze, Jean-François
Gunawan, Rudiyanto
Paldi, Andras
author_sort Parmentier, Romuald
collection PubMed
description When human cord blood–derived CD34+ cells are induced to differentiate, they undergo rapid and dynamic morphological and molecular transformations that are critical for fate commitment. In particular, the cells pass through a transitory phase known as “multilineage-primed” state. These cells are characterized by a mixed gene expression profile, different in each cell, with the coexpression of many genes characteristic for concurrent cell lineages. The aim of our study is to understand the mechanisms of the establishment and the exit from this transitory state. We investigated this issue using single-cell RNA sequencing and ATAC-seq. Two phases were detected. The first phase is a rapid and global chromatin decompaction that makes most of the gene promoters in the genome accessible for transcription. It results 24 h later in enhanced and pervasive transcription of the genome leading to the concomitant increase in the cell-to-cell variability of transcriptional profiles. The second phase is the exit from the multilineage-primed phase marked by a slow chromatin closure and a subsequent overall down-regulation of gene transcription. This process is selective and results in the emergence of coherent expression profiles corresponding to distinct cell subpopulations. The typical time scale of these events spans 48 to 72 h. These observations suggest that the nonspecificity of genome decompaction is the condition for the generation of a highly variable multilineage expression profile. The nonspecific phase is followed by specific regulatory actions that stabilize and maintain the activity of key genes, while the rest of the genome becomes repressed again by the chromatin recompaction. Thus, the initiation of differentiation is reminiscent of a constrained optimization process that associates the spontaneous generation of gene expression diversity to subsequent regulatory actions that maintain the activity of some genes, while the rest of the genome sinks back to the repressive closed chromatin state.
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spelling pubmed-96049492022-10-27 Global genome decompaction leads to stochastic activation of gene expression as a first step toward fate commitment in human hematopoietic cells Parmentier, Romuald Racine, Laëtitia Moussy, Alice Chantalat, Sophie Sudharshan, Ravi Papili Gao, Nan Stockholm, Daniel Corre, Guillaume Fourel, Geneviève Deleuze, Jean-François Gunawan, Rudiyanto Paldi, Andras PLoS Biol Research Article When human cord blood–derived CD34+ cells are induced to differentiate, they undergo rapid and dynamic morphological and molecular transformations that are critical for fate commitment. In particular, the cells pass through a transitory phase known as “multilineage-primed” state. These cells are characterized by a mixed gene expression profile, different in each cell, with the coexpression of many genes characteristic for concurrent cell lineages. The aim of our study is to understand the mechanisms of the establishment and the exit from this transitory state. We investigated this issue using single-cell RNA sequencing and ATAC-seq. Two phases were detected. The first phase is a rapid and global chromatin decompaction that makes most of the gene promoters in the genome accessible for transcription. It results 24 h later in enhanced and pervasive transcription of the genome leading to the concomitant increase in the cell-to-cell variability of transcriptional profiles. The second phase is the exit from the multilineage-primed phase marked by a slow chromatin closure and a subsequent overall down-regulation of gene transcription. This process is selective and results in the emergence of coherent expression profiles corresponding to distinct cell subpopulations. The typical time scale of these events spans 48 to 72 h. These observations suggest that the nonspecificity of genome decompaction is the condition for the generation of a highly variable multilineage expression profile. The nonspecific phase is followed by specific regulatory actions that stabilize and maintain the activity of key genes, while the rest of the genome becomes repressed again by the chromatin recompaction. Thus, the initiation of differentiation is reminiscent of a constrained optimization process that associates the spontaneous generation of gene expression diversity to subsequent regulatory actions that maintain the activity of some genes, while the rest of the genome sinks back to the repressive closed chromatin state. Public Library of Science 2022-10-26 /pmc/articles/PMC9604949/ /pubmed/36288293 http://dx.doi.org/10.1371/journal.pbio.3001849 Text en © 2022 Parmentier et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Parmentier, Romuald
Racine, Laëtitia
Moussy, Alice
Chantalat, Sophie
Sudharshan, Ravi
Papili Gao, Nan
Stockholm, Daniel
Corre, Guillaume
Fourel, Geneviève
Deleuze, Jean-François
Gunawan, Rudiyanto
Paldi, Andras
Global genome decompaction leads to stochastic activation of gene expression as a first step toward fate commitment in human hematopoietic cells
title Global genome decompaction leads to stochastic activation of gene expression as a first step toward fate commitment in human hematopoietic cells
title_full Global genome decompaction leads to stochastic activation of gene expression as a first step toward fate commitment in human hematopoietic cells
title_fullStr Global genome decompaction leads to stochastic activation of gene expression as a first step toward fate commitment in human hematopoietic cells
title_full_unstemmed Global genome decompaction leads to stochastic activation of gene expression as a first step toward fate commitment in human hematopoietic cells
title_short Global genome decompaction leads to stochastic activation of gene expression as a first step toward fate commitment in human hematopoietic cells
title_sort global genome decompaction leads to stochastic activation of gene expression as a first step toward fate commitment in human hematopoietic cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604949/
https://www.ncbi.nlm.nih.gov/pubmed/36288293
http://dx.doi.org/10.1371/journal.pbio.3001849
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