TY  - JOUR
A1  - Rosales-Alvarez, Reyna Edith
A1  - Rettkowski, Jasmin
A1  - Herman, Josip Stefan
A1  - Dumbović, Gabrijela
A1  - Cabezas-Wallscheid, Nina
A1  - Grün, Dominic
T1  - VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells
JF  - Genome Biology
N2  - 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.
KW  - gene expression noise
KW  - single-cell RNA sequencing
KW  - stem cell differentiation
KW  - cell sate variability
KW  - ageing
KW  - hematopoietic stem cells
KW  - machine learning
KW  - mathematical modeling
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358042
VL  - 24
ER  -