VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells

Variability of gene expression due to stochasticity of transcription or variation of extrinsic signals, termed biological noise, is a potential driving force of cellular differentiation. Utilizing single-cell RNA-sequencing, we develop VarID2 for the quantification of biological noise at single-cell...

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Autores principales: Rosales-Alvarez, Reyna Edith, Rettkowski, Jasmin, Herman, Josip Stefan, Dumbović, Gabrijela, Cabezas-Wallscheid, Nina, Grün, Dominic
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Method
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10290360/
https://www.ncbi.nlm.nih.gov/pubmed/37353813
http://dx.doi.org/10.1186/s13059-023-02974-1
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author Rosales-Alvarez, Reyna Edith
Rettkowski, Jasmin
Herman, Josip Stefan
Dumbović, Gabrijela
Cabezas-Wallscheid, Nina
Grün, Dominic
author_facet Rosales-Alvarez, Reyna Edith
Rettkowski, Jasmin
Herman, Josip Stefan
Dumbović, Gabrijela
Cabezas-Wallscheid, Nina
Grün, Dominic
author_sort Rosales-Alvarez, Reyna Edith
collection PubMed
description Variability of gene expression due to stochasticity of transcription or variation of extrinsic signals, termed biological noise, is a potential driving force of cellular differentiation. Utilizing single-cell RNA-sequencing, we develop VarID2 for the quantification of biological noise at single-cell resolution. VarID2 reveals enhanced nuclear versus cytoplasmic noise, and distinct regulatory modes stratified by correlation between noise, expression, and chromatin accessibility. Noise levels are minimal in murine hematopoietic stem cells (HSCs) and increase during differentiation and ageing. Differential noise identifies myeloid-biased Dlk1+ long-term HSCs in aged mice with enhanced quiescence and self-renewal capacity. VarID2 reveals noise dynamics invisible to conventional single-cell transcriptome analysis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-023-02974-1.
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spelling pubmed-102903602023-06-25 VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells Rosales-Alvarez, Reyna Edith Rettkowski, Jasmin Herman, Josip Stefan Dumbović, Gabrijela Cabezas-Wallscheid, Nina Grün, Dominic Genome Biol Method Variability of gene expression due to stochasticity of transcription or variation of extrinsic signals, termed biological noise, is a potential driving force of cellular differentiation. Utilizing single-cell RNA-sequencing, we develop VarID2 for the quantification of biological noise at single-cell resolution. VarID2 reveals enhanced nuclear versus cytoplasmic noise, and distinct regulatory modes stratified by correlation between noise, expression, and chromatin accessibility. Noise levels are minimal in murine hematopoietic stem cells (HSCs) and increase during differentiation and ageing. Differential noise identifies myeloid-biased Dlk1+ long-term HSCs in aged mice with enhanced quiescence and self-renewal capacity. VarID2 reveals noise dynamics invisible to conventional single-cell transcriptome analysis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-023-02974-1. BioMed Central 2023-06-23 /pmc/articles/PMC10290360/ /pubmed/37353813 http://dx.doi.org/10.1186/s13059-023-02974-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Method
Rosales-Alvarez, Reyna Edith
Rettkowski, Jasmin
Herman, Josip Stefan
Dumbović, Gabrijela
Cabezas-Wallscheid, Nina
Grün, Dominic
VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells
title VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells
title_full VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells
title_fullStr VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells
title_full_unstemmed VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells
title_short VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells
title_sort varid2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10290360/
https://www.ncbi.nlm.nih.gov/pubmed/37353813
http://dx.doi.org/10.1186/s13059-023-02974-1
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