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Seminar Series – “Delineating the Heterogeneity and Regulation of Astrocytes in Spinal Cord Injury”

Event Details:
Seminar Flyer - Jiaqian Wu

Summary:
To better understand the functions and interactions of the complex cell types in the brain, we have previously purified representative populations of neurons, astrocytes, oligodendrocyte precursor cells, newly formed oligodendrocytes, myelinating oligodendrocytes, microglia, endothelial cells, and pericytes from mouse cerebral cortex. We generated a transcriptome database for these cell types by RNA sequencing, including not only coding but also long non-coding RNAs (lncRNAs; >200 bp) which are regulatory RNAs playing important roles in the CNS. This database is widely used by the neuroscience community (https://www.brainrnaseq.org; http://jiaqianwulab.org/resource.htm). Recently, we have comprehensively investigated the molecular changes in the injury environment and the astrocyte-specific responses by isolating astrocyte lineage cells from injured adult spinal cords from acute to chronic stages. Bioinformatic and functional analyses identified a highly conserved lncRNA Zeb2os significantly upregulated in astrocytes after injury, and we demonstrated it plays an essential role in reactive astrogliosis and scar formation through the Zeb2os/Zeb2/Stat3 axis. Viral mediated knockdown of Zeb2os in subacute stage of spinal cord injury (SCI) led to reduced astrogliosis, lesion size and pSTAT3 in injured animal models. These studies unveiled the molecular basis of reactive astrogliosis and fill the knowledge gap regarding the functions of lncRNA in astrogliosis and SCI.
Currently, we are dissecting the heterogeneity of astrocyte lineage cells in SCI by single-cell RNA-sequencing. We found subpopulations with distinct functional enrichment and their identities defined by subpopulation-specific transcription factors and regulons. Immunohistochemistry (IHC) and RNAscope experiments and quantification by stereology verified the molecular signature, location and morphologies of potential resident neural progenitors or neural stem cells in the adult spinal cord before and after injury, and uncovered the previously undescribed populations. This study reveals new insights in the heterogeneity and cell state transition of glial progenitors in adult spinal cord before and after injury.