Deciphering cellular and functional heterogeneity in ageing blood
Nirmala Arul Rayan1, Debarka Sengupta2, Michelle Lim Gek1 and Shyam Prabhakar1
1Computational and Systems Biology, Genome Institute of Singapore.Singapore-138672;
2III-T, Computational Biology, Delhi, India- 110020
Ageing blood is highly heterogeneous, with diverse populations displaying distinct cell fate, abundance, growth and differentiation states (Dykstra and de Haan 2008; Geiger et al. 2013). Systematic transcriptional dysregulation are thought to underlie these age-related phenotypes (Horvath 2013; Benayoun et al. 2015). It is thus extremely important that we characterize such molecular dimensions of ageing in detail, in order to devise more precise diagnostics and interventions for extending the healthy lifespan. However, existing studies aimed at characterizing epigenetic perturbations are highly underpowered (Benayoun et al. 2015). Moreover, the experimental and computational technologies required for unbiased analysis of cellular heterogeneity in ageing immune cells have only recently been developed. Lastly, most existing cohort-scale studies of ageing focus on Western populations (Erikson et al. 2016) - they thus provide limited insight into the genetic and environmental determinants of healthy ageing in the Asian context. We performed an unbiased analysis of heterogeneity in blood cells from the old and young population using RNA-seq profiling of single cells. We analyse ~2000 single cells using a non-parametric method (Debarka et al. 2016 bioRXV) and a normalization technique that substantially reduces technical variability and improves the quality of downstream analyses. We used RCA’s (Li et al. 2017, Nat Genet) reference-based cell-cell similarity scores to robustly cluster them into major populations and their subtypes. Our study highlights pathways and key effector cell types modulating ageing, which could potentially facilitate novel drug targets for reversing changes associated with ageing and extend healthy lifespan.