mTORC2/RICTOR exerts differential levels of metabolic control in human embryonic, mesenchymal and neural stem cells

Stem cells, including pluripotent stem cells and adult stem cells, possess the remarkable capability of being able to self-renew while at the same time having potential to differentiate into different cell lineages and functionally distinct cell types. Human embryonic stem cells (hESCs) can differentiate into all adult stem cell types, including human mesenchymal stem cells (hMSCs) and human neural stem cells (hNSCs), but can also give rise to all terminally differentiated cell types (Wang et al., 2021a). Through the continuous replenishment of differentiated cells, stem cells support tissue homeostasis and respond to tissue injuries. Given the promising applications of stem cells in cell therapy and regenerative medicine, insights into molecular events underlying stem cell maintenance, self-renewal ability and pluripotency, continue to garner strong interest (Shan et al., 2021). Although metabolic pathways have been implicated in the reciprocal regulations of stem cell self-renewal and differentiation as well as organ homeostatic maintenance (Garcia-Prat et al., 2017), central aspects of how metabolic requirements differ and are regulated across the various types of human stem cells in our body remain enigmatic.