Moore Alex, Chinnaiya Kavitha, Kim Dong Won, Brown Sarah, Stewart Iain, Robins Sarah, Dowsett Georgina K C, Muir Charlotte, Travaglio Marco, Lewis Jo E, Ebling Fran, Blackshaw Seth, Furley Andrew, Placzek Marysia
School of Biosciences, The University of Sheffield, Sheffield, United Kingdom.
Bateson Centre, The University of Sheffield, Sheffield, United Kingdom.
Front Neurosci. 2022 Apr 7;16:832961. doi: 10.3389/fnins.2022.832961. eCollection 2022.
Hypothalamic tanycytes are neural stem and progenitor cells, but little is known of how they are regulated. Here we provide evidence that the cell adhesion molecule, NrCAM, regulates tanycytes in the adult niche. NrCAM is strongly expressed in adult mouse tanycytes. Immunohistochemical and hybridization analysis revealed that NrCAM loss of function leads to both a reduced number of tanycytes and reduced expression of tanycyte-specific cell markers, along with a small reduction in tyrosine hydroxylase-positive arcuate neurons. Similar analyses of NrCAM mutants at E16 identify few changes in gene expression or cell composition, indicating that NrCAM regulates tanycytes, rather than early embryonic hypothalamic development. Neurosphere and organotypic assays support the idea that NrCAM governs cellular homeostasis. Single-cell RNA sequencing (scRNA-Seq) shows that tanycyte-specific genes, including a number that are implicated in thyroid hormone metabolism, show reduced expression in the mutant mouse. However, the mild tanycyte depletion and loss of markers observed in NrCAM-deficient mice were associated with only a subtle metabolic phenotype.
下丘脑伸长细胞是神经干细胞和祖细胞，但对其调控方式知之甚少。在此，我们提供证据表明，细胞粘附分子NrCAM在成年生态位中调控伸长细胞。NrCAM在成年小鼠伸长细胞中强烈表达。免疫组织化学和杂交分析显示，NrCAM功能丧失导致伸长细胞数量减少、伸长细胞特异性细胞标志物表达降低，同时酪氨酸羟化酶阳性的弓状神经元略有减少。对E16期NrCAM突变体的类似分析表明，基因表达或细胞组成几乎没有变化，这表明NrCAM调控伸长细胞，而非早期胚胎下丘脑发育。神经球和器官型分析支持NrCAM控制细胞稳态的观点。单细胞RNA测序（scRNA-Seq）表明，包括一些与甲状腺激素代谢有关的伸长细胞特异性基因，在突变小鼠中表达降低。然而，在NrCAM缺陷小鼠中观察到的轻度伸长细胞耗竭和标志物丧失仅与轻微的代谢表型相关。
