摘要
Spinal cord injury(SCI)involves diverse injury responses in different cell types in a temporally and spatially specific manner.Here,using single-cell transcriptomic analyses combined with classic anatomical,behavioral,electrophysiological analyses,we report,with single-cell resolution,temporal molecular and cellular changes in crush-injured adult mouse spinal cord.Data revealed pathological changes of 12 different major cell types,three of which infiltrated into the spinal cord at distinct times post-injury.We discovered novel microglia and astrocyte subtypes in the uninjured spinal cord,and their dynamic conversions into additional stage-specific subtypes/states.Most dynamic changes occur at 3-days post-injury and by day-14 the second wave of microglial activation emerged,accompanied with changes in various cell types including neurons,indicative of the second round of attacks.By day-38,major cell types are still substantially deviated from uninjured states,demonstrating prolonged alterations.This study provides a comprehensive mapping of cellular/molecular pathological changes along the temporal axis after SCI,which may facilitate the development of novel therapeutic strategies,including those targeting microglia.
基金
grants from the National Key Research and Development Program of China(No.2016YFA0100800)
the International(regional)cooperation and communication program of the National Natural Science Foundation of China(No.81820108013,31620103904,82030035)
the State Key Program of the National Natural Science Foundation of China(No.81330030).