Population-specific heterogeneity in ontogeny of the broadly-conserved blood transcriptional program during the first week of life

Abstract

Previous research has shown that immune development during the first week of life, i.e. ontogeny, is progressive, consistent and robust, involving large numbers of differentially expressed genes at each sampled time point. To obtain more granular detail about conserved and population-specific ontogeny, the influence of day of life on blood gene expression and cell type composition was examined in two distinct neonatal populations, from The Gambia and Papua New Guinea, employing block randomization strategies to minimize batch effects. This enabled more detailed conclusions about ontogenic program differences between the two cohorts. Population-specific ontogeny revealed mechanistic insights likely to contribute to inherent population-based heterogeneity in the efficiency of neonatal immune responses, including cell cycle, kinesins, and DAP12 signaling in Papua New Guinea, and antigen presentation, clathrin-mediated endocytosis and alpha-defensins in The Gambia. Differences between populations interconnect using protein:protein interaction networks of population-specific genes and pathinkR-based pathway networks and heat maps, thus fitting the concept of pathway/network remodeling. In addition to the population-specific changes, there is a profound core ontogenic gene-expression program involving ~18% of all expressed genes with remarkable 88-96% conservation at each day of life, revealing new contributors to this shared early-life ontogenic program.