Single cell RNA-sequencing reveals five subtypes of olfactory bulb-derived olfactory ensheathing cells that secrete Reelin

Olfactory ensheathing cells (OECs) are the only glial cells that support the olfactory sensory neurons which undergo adult neurogenesis and continually project their axons to glomeruli in the olfactory bulbs. We used single cell RNA sequencing to study the gene expression programs of OECs and to determine the diversity of purified OECs previously shown to promote spinal cord injury repair. Our analyses revealed five subtypes of OECs, each expressing unique marker genes and pathways indicative of progenitor, axonal regeneration, migration, or microglia-like functions. As expected, we found substantial overlap of OEC genes with those of Schwann cells, but also with astrocytes, oligodendrocytes and microglia. We experimentally confirmed the classic marker genes of the OEC subtypes and provide evidence that Reelin and Connective Tissue Growth Factors are secreted by multiple OEC subtypes. Our results support that adult OECs are a hybrid glia including some with progenitor characteristics and that they likely carry out diverse functions related to injury repair and axonal regeneration.嗅鞘细胞（Olfactory ensheathing cells, OECs）是唯一一类能够支持嗅觉感觉神经元的胶质细胞：此类神经元可发生成体神经发生，并持续将轴突投射至嗅球的肾小球结构。本研究采用单细胞RNA测序技术，分析纯化嗅鞘细胞的基因表达程序，并解析其亚型多样性——既往研究已证实，这类细胞可促进脊髓损伤修复。分析结果显示，嗅鞘细胞可分为五种亚型，各亚型均表达独特的标记基因，并分别对应祖细胞、轴突再生、迁移或类小胶质细胞的功能通路。正如预期，本研究发现嗅鞘细胞的基因表达谱与施万细胞存在大量重叠，同时也与星形胶质细胞、少突胶质细胞及小胶质细胞存在基因表达重叠。我们通过实验验证了各嗅鞘细胞亚型的经典标记基因，并证实Reelin与结缔组织生长因子可由多种嗅鞘细胞亚型分泌。本研究结果支持：成体嗅鞘细胞属于一类混合型胶质细胞，其中部分亚型具备祖细胞特性，且其功能可能与损伤修复及轴突再生密切相关。