Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
Department of Biochemistry and Biophysics, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Stockholm University, 17165 Stockholm, Sweden.
Dev Cell. 2023 Oct 23;58(20):2140-2162.e5. doi: 10.1016/j.devcel.2023.07.015. Epub 2023 Aug 16.
A wealth of specialized cell populations within the skin facilitates its hair-producing, protective, sensory, and thermoregulatory functions. How the vast cell-type diversity and tissue architecture develops is largely unexplored. Here, with single-cell transcriptomics, spatial cell-type assignment, and cell-lineage tracing, we deconstruct early embryonic mouse skin during the key transitions from seemingly uniform developmental precursor states to a multilayered, multilineage epithelium, and complex dermal identity. We identify the spatiotemporal emergence of hair-follicle-inducing, muscle-supportive, and fascia-forming fibroblasts. We also demonstrate the formation of the panniculus carnosus muscle (PCM), sprouting blood vessels without pericyte coverage, and the earliest residence of mast and dendritic immune cells in skin. Finally, we identify an unexpected epithelial heterogeneity within the early single-layered epidermis and a signaling-rich periderm layer. Overall, this cellular and molecular blueprint of early skin development-which can be explored at https://kasperlab.org/tools-establishes histological landmarks and highlights unprecedented dynamic interactions among skin cells.
皮肤中丰富的特化细胞群体使其具有产生毛发、保护、感知和体温调节等功能。大量细胞类型多样性和组织架构如何发育在很大程度上仍是未知的。在这里，我们通过单细胞转录组学、空间细胞类型分配和细胞谱系追踪，对早期胚胎小鼠皮肤进行了解构，这些皮肤经历了从看似均匀的发育前体状态到多层、多谱系上皮和复杂真皮特征的关键转变。我们确定了毛发囊诱导、肌肉支持和筋膜形成成纤维细胞的时空出现。我们还证明了在没有周细胞覆盖的情况下形成了脂肪垫肌 (PCM)、血管发芽，以及最早驻留在皮肤中的肥大细胞和树突状免疫细胞。最后，我们在早期单层表皮内发现了意想不到的上皮异质性和富含信号的表皮层。总的来说，这个早期皮肤发育的细胞和分子蓝图可以在 https://kasperlab.org/tools 上进行探索，它建立了组织学标志，并突出了皮肤细胞之间前所未有的动态相互作用。
