The Development And Features Of Adult-born Neurons In Mouse Olfactory Bulb Via The Integration Of Single-cell Transcriptomes

Objectives:The adult neurogenesis from subventricular zone is a portion of plasticity of micro neural circuitries in the mouse olfactory bulb.We detected the development and features of adult-born neurons in mouse olfactory bulb and discussed the feasibility of its positioning and separation through the integration of single-cell transcriptomes based on the adult neurogenesis making an attempt to support the related research in the fields of nervous system regeneration and repair and plasticity of neural circuit.Methods:We collected and filtered the datasets of single-cell transcriptomes from mouse olfactory bulb and subventricular zone.The datasets were mapped and annotated with the databases of bioinformatics after preprocessing.The expression matrix was constructed and corrected via the screening workflow.Subsequently,we detected the types and subtypes of cells through the effective dimensionality reduction and clustering algorithms.The differential expression among cell groups was tested via the statistical test method.The pseudotime of cytogenesis trajectory was modeled computationally based on the results of dimensionality reduction and cell correlation.Furthemore,we constructed the co-expression modules and networks of genes which were timing-dependent and enriched the biological functions of each module via the Gene Ontology database.Results:Through the integration of 3 datasets of single-cell transcriptome data,a total of 96,732 cells and 27,375 genes were obtained.We identified 27 cell groups,4 subtype of astrocyte and 5 subtypes of neuron in olfactory bulb.The trajectories of neurogenesis and oligodendrogenesis were observed through the results of dimensionality reduction.We obtained 3,023 genes related to the trajectory of neurogenesis and 1,470 genes related to the trajectory of oligodendrogenesis via pseudotime analysis.13 co-expression modules of neurogenesis and 10 co-expression modules of oligodendrogenesis were constructed respectively according to the correlations of expression.Ultimately,3 molecular characteristics of adult-born neurons in mouse olfactory bulb were obtained via comparing the expression profile with the results of in situ hybridization which has the potential as marker.Conclusions:The adult neurogenesis.The dedifferentiation was obtained when astrocytes developed into NPC or OPC as the source of adult neurogenesis associated with mouse olfactory bulb.Secondarily,rather than the expression profile represent the features of oligodendrocyte during the transformation of astrocytes to OPC,the development of NPC represent proliferation-related characteristics barely at the initial stage.The features of neural transformation began to appear when TAP.The Ptprd-related regulatory processes may participate in the adhesion of axons to oligodendrocytes and regulated the formation of myelin.The variation of expression among the transformation of activated NSC to TAP mainly involved the enhancement of mitosis and the decreasing of glial cell characteristics.The neural differentiation-related processes were activated and immature neural markers occurred through the regulation of Sox family-related pathways among the NB generated in the proliferation of TAP.The retention of expression profile associated with mitosis-related pathways indicated that the NB had considerable ability of divide and proliferate at the early stage.The cell cycle-related processes of NB may be regulated through the Hmgb2-related pathways.During the migration,the proliferation-related processes such as cell cycle regulation tended to end and the expression profile began to shift to the process of neuronal differentiation such as neurite outgrowth and cell migration.The processes of cell adhesion and migration of adult-born neurons were related to the adhesion of membrane proteins such as Cldn5 and Bsg which regulated by Robo2,as well as the differentiation were inhibited via Tmsb4X and other related pathways.The differentiation and maturation of adult-born neurons were regulated through the calcium signal related to Calm2 after the migration to olfactory bulb.These regulated processes mainly included neurite extension,synapse formation and transport of synaptic vesicle.The radial migration of adult-born neurons into the neural microcircuit may related to Prok2 and other pathways regulated via olfactory activity.In addition,the membrane receptor protein Prokr2 with high cell specificity among these molecular characteristics could be used for sorting and obtaining of adult-born neurons in mouse olfactory bulb.