Integrated Transcriptomic and Proteomic Analysis of Human Eccrine Sweat Glands Identifies Missing and Novel Proteins[S]

This study reports the first in-depth RNA and protein expression profiles of human sweat glands. RNA-sequencing and proteomic analysis were performed on ∼250 sweat glands collected from a healthy individual. Data revealed ∼13,300 protein-coding genes, ∼53,400 non-coding genes, and ∼6,100 proteins are expressed in eccrine sweat glands. Also, two missing and five novel proteins were identified. Integrated transcriptome and protein expression profile of eccrine sweat gland can be used to study the etiology of many diseases relevant to the sweat gland. [Display omitted] Highlights •RNA-seq and proteome analysis of human eccrine sweat glands were conducted.•Approximately 138,000 transcripts and ∼6,100 proteins were identified.•Proteins involved in secretion, reabsorption, and wound healing identified.•Two missing and five novel proteins were identified. The eccrine sweat gland is an exocrine gland that is involved in the secretion of sweat for control of temperature. Malfunction of the sweat glands can result in disorders such as miliaria, hyperhidrosis and bromhidrosis. Understanding the transcriptome and proteome of sweat glands is important for understanding their physiology and role in diseases. However, no systematic transcriptome or proteome analysis of sweat glands has yet been reported. Here, we isolated eccrine sweat glands from human skin by microdissection and performed RNA-seq and proteome analysis. In total, ∼138,000 transcripts and ∼6,100 proteins were identified. Comparison of the RNA-seq data of eccrine sweat glands to other human tissues revealed the closest resemblance to the cortex region of kidneys. The proteome data showed enrichment of proteins involved in secretion, reabsorption, and wound healing. Importantly, protein level identification of the calcium ion channel TRPV4 suggests the importance of eccrine sweat glands in re-epithelialization of wounds and prevention of dehydration. We also identified 2 previously missing proteins from our analysis. Using a proteogenomic approach, we identified 7 peptides from 5 novel genes, which we validated using synthetic peptides. Most of the novel proteins were from short open reading frames (sORFs) suggesting that many sORFs still remain to be annotated in the human genome. This study presents the first integrated analysis of the transcriptome and proteome of the human eccrine sweat gland and would become a valuable resource for studying sweat glands in physiology and disease.