PDF(Pubmed)
Abstract：
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 via 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.
摘要：
皮脂腺（SG）及其油性分泌物（皮脂）对于维持皮肤结构和功能是必不可少的，并且它们的放松调节导致皮肤病症,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的进行性转录变化从未被详细描述过。这里,我们利用皮脂腺增生和综合空间转录组学提供的高细胞分辨率，伪时间分析，RNA速度，和功能富集，利用空间转录组学绘制皮脂腺分化景观图。通过与已发表的SG转录组数据进行比较来验证我们的结果，并通过评估公共储存库HumanProteinAtlas中转录本子集的蛋白质表达模式来进一步证实。从无监督聚类产生的四个皮脂腺细胞分化阶段出发，我们展示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通过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。我们的报告由免费提供和可浏览的在线工具补充。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。
