Spatiotemporal orchestration of multicellular transcriptional programs and communications in the early stage of spinal cord injury

Abstract

The spinal cord is an assembly of spatially organized multicomponent cells that coordinates the transmission of motor, sensory and autonomic nerve functions. Although complex pathological and cellular alterations in spinal cord injury (SCI) have been documented, the spatiotemporal architecture of the molecular events that drive the injury progression remains poorly understood. Here, we conducted a spatially resolved transcriptomic profiling of gene expression in a mouse model of SCI, which demonstrated the comprehensive gene co-expression networks and transcriptional programs underlying the anatomic disorganization induced by SCI. Further, with integration of the single-cell RNA-sequencing datasets, we delineated the exquisite orchestration of multicellular transcriptional programs and in situ cell-cell interactions following SCI, and discerned regional diversity of astrocyte populations in intact and injured spinal tissues. The spatial molecular features endow the cell types with new biological significance, showcased by the identification of a distinct, SCI-induced population of astrocytes that exhibit functional heterogeneity in promoting both beneficial neuro/synapto-supportive and deleterious pro-inflammatory programs. Together, our dataset and analysis provide a rich resource and a spatiotemporal molecular atlas that potentially disentangle the cell organization in mammalian SCI and advance the injury management.