Single-cell RNA-seq Analysis of PBMCs of Three Cameroonian Populations Reveals Differences in Cell Type Distribution as Well as Differentially Expressed Genes

Abstract Text: Current understanding of the human immune system is mostly based on studies of individuals of Eurasian ancestry in westernized settings. Sub-Saharan African populations with great genetic diversity are underrepresented, which leads to gaps in our understanding and treatment of immune-based diseases in individuals of African ancestry. To address this disparity, we performed single-cell RNA-seq analysis on unstimulated and stimulated peripheral blood mononuclear cells (PBMCs) of 160 individuals from three diverse indigenous populations in Cameroon: the Baka/ Bagyeli rainforest hunter-gatherers (RHGs), Fulani pastoralists and Tikari agriculturalists.
First results of our study reveal differences in cell type distribution at baseline, for example an expanded cytotoxic T cell population in the RHGs, who live in a high pathogen environment, compared to the Fulani and Tikari. Additionally, we identify quantitative and qualitative differences in differentially expressed genes (DEGs) in PBMCs. For instance, in age-associated B cells at baseline we find 187 DEGs between RHGs compared to Tikari compared to 104 DEGs between Fulani and Tikari. The specific DEGs with the greatest fold change differ, between RHGs and Tikari - LGMN is upregulated in the RHGs, whereas between Fulani and Tikari TMEM163 is upregulated in the Fulani.
Our findings delineate variation in immune cells at baseline between populations and emphasize the need to take ancestry into consideration when treating individuals with immune diseases or using immune-based therapeutics.

We are currently investigating the genetic variants that contribute to this expression variation by linking epigenetic features (ATAC-seq) with gene expression in the same cell (RNA-seq) in PBMCs.