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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Detalles Bibliográficos
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
Descripción
Sumario: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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