Department of Dermatology, University of California, San Francisco and Veterans Affairs Medical Center, San Francisco, CA, USA.
Nantomics, LLC, Culver City, CA, USA.
Cell Rep. 2018 Oct 23;25(4):871-883. doi: 10.1016/j.celrep.2018.09.006.
Perturbations in the transcriptional programs specifying epidermal differentiation cause diverse skin pathologies ranging from impaired barrier function to inflammatory skin disease. However, the global scope and organization of this complex cellular program remain undefined. Here we report single-cell RNA sequencing profiles of 92,889 human epidermal cells from 9 normal and 3 inflamed skin samples. Transcriptomics-derived keratinocyte subpopulations reflect classic epidermal strata but also sharply compartmentalize epithelial functions such as cell-cell communication, inflammation, and WNT pathway modulation. In keratinocytes, ∼12% of assessed transcript expression varies in coordinate patterns, revealing undescribed gene expression programs governing epidermal homeostasis. We also identify molecular fingerprints of inflammatory skin states, including S100 activation in the interfollicular epidermis of normal scalp, enrichment of a CD1CCD301A myeloid dendritic cell population in psoriatic epidermis, and IL1βCCL3CD14 monocyte-derived macrophages enriched in foreskin. This compendium of RNA profiles provides a critical step toward elucidating epidermal diseases of development, differentiation, and inflammation.
转录程序的干扰会导致各种皮肤病理，从受损的屏障功能到炎症性皮肤病。然而，这个复杂的细胞程序的全局范围和组织仍然没有定义。在这里，我们报告了来自 9 个正常和 3 个炎症皮肤样本的 92889 个人类表皮细胞的单细胞 RNA 测序图谱。基于转录组学的角蛋白细胞亚群反映了经典的表皮层，但也将上皮细胞的功能（如细胞间通讯、炎症和 WNT 途径调节）进行了精细分区。在角蛋白细胞中，约 12%的评估转录表达以协调的模式变化，揭示了控制表皮稳态的未描述的基因表达程序。我们还鉴定了炎症性皮肤状态的分子特征，包括正常头皮滤泡间表皮中 S100 的激活，银屑病表皮中 CD1CCD301A 髓样树突状细胞群体的富集，以及富含 IL1βCCL3CD14 单核细胞衍生的巨噬细胞的包皮。这个 RNA 图谱的汇编为阐明发育、分化和炎症的表皮疾病提供了关键的一步。
