We are dedicated to understanding the mysterious stage during oligodendrocyte development. In order to become myelinating oligodendrocytes, oligodendrocyte precursor cells (OPCs) must stop proliferation and differentiate into an intermediate stage, called “pre-myelinating” oligodendrocytes. Pre-myelinating oligodendrocytes can only exist transiently (about 2-3 days in vitro and in vivo); they either become mature oligodendrocyte or undergo programmed cell death. Intriguingly, pre-myelinating oligodendrocytes start expressing large amounts of myelin RNAs and rapidly change their cellular machineries and morphologies. Our previous work has identified a critical intrinsic pathway governing pre-myelinating oligodendrocyte survival (Sun et al., Cell 2018), yet how do pre-myelinating oligodendrocytes sense and integrate nutrients, axonal contact, and intracellular stress cues remains unanswered.
We are using mouse genetics, genome-wide CRISPR/Cas screen, and live-cell imaging approach to address this question. In addition, we are taking advantage of pre-myelinating oligodendrocytes as a new model system to study cell death, stress responses, and autophagy to uncover new aspects of cell metabolism. Finally, we are developing genetic tools for targeting, labeling, and manipulation of pre-myelinating oligodendrocytes. Together this work will be valuable in studying oligodendrocyte development and further determining physiological function of pre-myelinating oligodendrocytes in developmental and myelin repair.