GSE127253
Post-transcriptional mechanisms distinguish human and chimpanzee forebrain progenitors
The forebrain has expanded in size and complexity during hominoid evolution. The contribution of post-transcriptional control of gene expression to this process is unclear. Using in-depth proteomics in combination with bulk and single-cell RNA sequencing, we analyzed protein and RNA levels of almost 5,000 genes in human and chimpanzee forebrain neural progenitor cells. We found that species differences in protein expression level was often independent of RNA levels, and more frequent than transcriptomic differences. Low-abundant proteins were more likely to show species-specific expression levels, while proteins expressed at a high level appeared to have evolved under stricter constraints. Our study implicates a previously unappreciated broad and important role for post-transcriptional regulatory mechanisms in the evolution of the human forebrain. Overall design: Bulk RNA-seq was performed on iPSC-derived forebrain neural progenitors at day 14 of differentiation from two human and two chimpanzee individuals, two differentiation replicates per line. For one human and one chimpanzee, bulk RNA-seq was also performed at day 13, 15, and 16 of differentiation, two differentiation replicates per line. Single cell RNA-seq was done for one human and one chimpanzee individual, with one differentiation replicate.