Description

Single cell expression analysis of stem cell models of primate cerebral cortex development

Alessio Strano, Rick Livesey

Wellcome Trust/CRUK Gurdon Institute, University of Cambridge, Cambridge, UK

Differences in the overall size and total number of neurons in the cerebral cortex are two of the factors underlying differences in cognitive capacity among primates. Understanding the cellular and molecular mechanisms underpinning the differences in the number of neurons produced during cortical development has the potential to provide insights into the evolution of the hominoid brain. Our group has previously shown that cortical neural progenitor cells derived from pluripotent stem cells (PSCs) of different primate species recapitulate species-specific development in vivo. Specifically, we reported that cortical progenitor cell proliferation/differentiation dynamics and the timing of neurogenesis of different neuronal subtypes differs between smaller and larger-brained primates when studied in stem cell models. Notably, species-specific progenitor cell proliferative behaviours are largely controlled by cell-autonomous mechanisms. Single cell RNA sequencing has the potential to both characterise in detail the progenitor cell and neuron types generated during cortical development in vitro, as well as identifying cellular pathways underpinning species-specific progenitor cell proliferative behaviours. To investigate the genetic contributions underpinning these developmental differences we are performing single-cell RNA-seq in human and non-human primate PSC-derived cerebral cortex at different stages of development using the Drop-seq technology. We have found that stem cell-derived early stage human cortex contains a complex set of progenitor cell subtypes, and are currently extending these analyses to gorilla and chimpanzee to compare cell types among species.