Sebaceous glands (SG) and their oily secretion (sebum) are indispensable for maintaining skin structure and function, and their deregulation causes skin disorders including but not limited to acne. Recent studies also indicate that sebum may have important immunomodulatory activities and may influence whole-body energy metabolism. However, the progressive transcriptional changes of sebocytes that lead to sebum production have never been characterized in detail. Here, we exploited the high cellular resolution provided by sebaceous hyperplasia and integrated spatial transcriptomics, pseudo time analysis, RNA velocity, and functional enrichment to map the landscape of sebaceous differentiation. Our results were validated by comparison with published SG transcriptome data and further corroborated by assessing the protein expression pattern of a subset of the transcripts in the public repository Human Protein Atlas. Departing from four sebocyte differentiation stages generated by unsupervised clustering, we demonstrate consecutive modulation of cellular functions associable with specific gene sets, from cell proliferation and oxidative phosphorylation lipid synthesis to cell death. Both validation methods confirmed the biological significance of our results. Our report is complemented by a freely available and browsable online tool. Our data provide the first high-resolution spatial portrait of the SG transcriptional landscape and deliver starting points for experimentally assessing novel candidate molecules for regulating SG homeostasis in health and disease.

中文翻译：

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人类皮脂龟头转录程序的空间肖像


皮脂腺（SG）及其油性分泌物（皮脂）对于维持皮肤结构和功能不可或缺，其失调会导致皮肤疾病，包括但不限于痤疮。最近的研究还表明，皮脂可能具有重要的免疫调节活性，并可能影响全身能量代谢。然而，导致皮脂产生的皮脂细胞进行性转录变化从未得到详细描述。在这里，我们利用皮脂腺增生提供的高细胞分辨率，并整合空间转录组学、伪时间分析、RNA速度和功能富集来绘制皮脂腺分化的图谱。我们的结果通过与已发表的 SG 转录组数据进行比较得到验证，并通过评估公共存储库人类蛋白质图谱中转录子子集的蛋白质表达模式进一步证实。与无监督聚类产生的四个皮脂细胞分化阶段不同，我们证明了与特定基因集相关的细胞功能的连续调节，从细胞增殖和氧化磷酸化脂质合成到细胞死亡。两种验证方法都证实了我们结果的生物学意义。我们的报告得到了免费提供且可浏览的在线工具的补充。我们的数据提供了 SG 转录景观的第一个高分辨率空间肖像，并为实验评估用于调节健康和疾病中 SG 稳态的新型候选分子提供了起点。