The M3 Muscarinic Acetylcholine Receptor Promotes Epidermal Differentiation

The M3 muscarinic acetylcholine receptor (CHRM3) is predominantly expressed in the basal epidermal layer where it mediates the effects of the auto/paracrine cytotransmitter acetylcholine. Patients with the autoimmune blistering disease pemphigus develop autoantibodies to CHRM3 and show alterations in keratinocyte adhesion, proliferation and differentiation, suggesting that CHRM3 controls these cellular functions. Chrm3 mice display altered epidermal morphology resembling that seen in patients with pemphigus vulgaris. Here, we characterized the cellular and molecular mechanisms whereby CHRM3 controls epidermal structure and function. We used single cell (sc)RNA-seq to evaluate keratinocyte heterogeneity and identify differentially expressed genes in specific subpopulations of epidermal cells in Chrm3 KO neonatal mice.M3型毒蕈碱乙酰胆碱受体（CHRM3）主要在表皮基底层中表达，介导自分泌/旁分泌细胞递质乙酰胆碱的生物学效应。罹患自身免疫性大疱性疾病天疱疮的患者可产生针对CHRM3的自身抗体，且出现角质形成细胞黏附、增殖与分化异常，提示CHRM3可调控上述细胞功能。CHRM3敲除小鼠的表皮形态发生改变，其表型与寻常型天疱疮患者的表皮改变相似。本研究旨在阐明CHRM3调控表皮结构与功能的细胞及分子机制。我们采用单细胞RNA测序（scRNA-seq）技术，对CHRM3敲除新生小鼠表皮细胞的特定亚群中的角质形成细胞异质性进行评估，并鉴定差异表达基因。