PREGNANCY-RESPONSIVE POOLS OF ADULT NEURAL STEM CELLS FOR TRANSIENT NEUROGENESIS IN MOTHERS

Adult neural stem cells (NSCs) contribute to lifelong brain plasticity. In the adult mouse ventricular-subventricular zone, NSCs are heterogeneous and, depending on their location in the niche, give rise to different subtypes of olfactory bulb (OB) interneurons. Here we show that multiple regionally-distinct NSCs, including domains that are usually quiescent, are recruited on different gestation days during pregnancy. Synchronized activation of these adult NSC pools generates transient waves of short-lived OB interneurons, especially in layers with less neurogenesis under homeostasis. Using spatial transcriptomics, we identify molecular markers of pregnancy-associated interneurons, and show that some subsets are temporarily needed for own pup recognition. Thus, pregnancy triggers transient, yet behaviorally-relevant neurogenesis, highlighting the physiological relevance of adult stem cell heterogeneity. Comparative analysis between four mouse brain samples; (i) one mother during perinatal care, (ii) one mother at peri-weaning, (iii) two age-matched virgins, was performed with the 10x Genomics Visium platform for fresh frozen samples. Spatial transcriptome analysis focused on the differential gene expression across these states and was performed both globally and also stratified within the corresponding spot clusters.成年神经干细胞（adult neural stem cells，NSCs）介导终生大脑可塑性。在成年小鼠脑室下区（ventricular-subventricular zone，V-SVZ）中，成年神经干细胞具有异质性，且根据其在干细胞微环境（niche）中的位置差异，可分化为嗅球（olfactory bulb，OB）的不同亚型中间神经元。本研究发现，多个区域特征各异的成年神经干细胞（包括通常处于静息状态的区域）会在妊娠过程中的不同妊娠天数被招募激活。这些成年神经干细胞池的同步激活会产生短暂出现的短命嗅球中间神经元波，尤其在稳态条件下神经发生水平较低的脑层中更为显著。本研究利用空间转录组学（spatial transcriptomics）技术，鉴定出妊娠相关中间神经元的分子标志物，并证实部分神经元亚群对母鼠识别自身幼崽具有暂时性必需作用。综上，妊娠可触发短暂但与行为相关的神经发生过程，凸显了成体干细胞异质性的生理学意义。本研究采用10x Genomics Visium平台对新鲜冷冻样本进行检测，对4组小鼠脑组织样本开展比较分析：(i) 1只处于围产期护理阶段的母鼠，(ii) 1只处于断奶前后阶段的母鼠，(iii) 2只年龄匹配的未生育雌鼠。空间转录组分析聚焦于这些状态下的差异基因表达，既进行了全局分析，也在对应的测序斑点簇内开展了分层分析。