Translational Vascular Research, Department of Clinical Medicine, The Arctic University of Norway, 9019 Tromsø, Norway.
Science for Life Laboratory, Department of Protein Science, Royal Institute of Technology (KTH), 171 21 Stockholm, Sweden.
Cell Rep. 2022 Jul 12;40(2):111046. doi: 10.1016/j.celrep.2022.111046.
The importance of defining cell-type-specific genes is well acknowledged. Technological advances facilitate high-resolution sequencing of single cells, but practical challenges remain. Adipose tissue is composed primarily of adipocytes, large buoyant cells requiring extensive, artefact-generating processing for separation and analysis. Thus, adipocyte data are frequently absent from single-cell RNA sequencing (scRNA-seq) datasets, despite being the primary functional cell type. Here, we decipher cell-type-enriched transcriptomes from unfractionated human adipose tissue RNA-seq data. We profile all major constituent cell types, using 527 visceral adipose tissue (VAT) or 646 subcutaneous adipose tissue (SAT) samples, identifying over 2,300 cell-type-enriched transcripts. Sex-subset analysis uncovers a panel of male-only cell-type-enriched genes. By resolving expression profiles of genes differentially expressed between SAT and VAT, we identify mesothelial cells as the primary driver of this variation. This study provides an accessible method to profile cell-type-enriched transcriptomes using bulk RNA-seq, generating a roadmap for adipose tissue biology.
定义细胞类型特异性基因的重要性是众所周知的。技术进步促进了单细胞的高分辨率测序，但仍存在实际挑战。脂肪组织主要由脂肪细胞组成，这些大型浮质细胞需要进行广泛的、产生假象的处理，才能进行分离和分析。因此，尽管脂肪细胞是主要的功能细胞类型，但它们经常从单细胞 RNA 测序 (scRNA-seq) 数据集中缺失。在这里，我们从未分离的人脂肪组织 RNA-seq 数据中破译细胞类型特异性转录组。我们使用 527 个内脏脂肪组织 (VAT) 或 646 个皮下脂肪组织 (SAT) 样本对所有主要组成细胞类型进行了分析，鉴定出超过 2300 个细胞类型特异性转录本。性别亚组分析揭示了一组仅男性特异性的细胞类型特异性基因。通过解析 SAT 和 VAT 之间差异表达基因的表达谱，我们确定间皮细胞是这种变化的主要驱动因素。本研究提供了一种使用批量 RNA-seq 分析细胞类型特异性转录组的方法，为脂肪组织生物学生成了路线图。
