Revealing the Organ-Specific Expression of SPTBN1 using Single-Cell RNA Sequencing Analysis

Despite the recent technological advances in single-cell RNA sequencing, it is still unknown how three marker genes (SPTBN1, EPDR1, and PKDCC), which are associated with bone fractures and highly expressed in the muscle tissue, are contributing to the development of other tissues and organs at the cellular level. This study aims to analyze three marker genes at the single-cell level using 15 organ tissue types of adult human cell atlas (AHCA). The single-cell RNA sequencing analysis used three marker genes and a publicly available AHCA data set. AHCA data set contains more than 84,000 cells from 15 organ tissue types. Quality control filtering, dimensionality reduction, clustering for cells, and data visualization were performed using the Seurat package. A total of 15 organ types are included in the downloaded data sets: Bladder, Blood, Common Bile Duct, Esophagus, Heart, Liver, Lymph Node, Marrow, Muscle, Rectum, Skin, Small Intestine, Spleen, Stomach, and Trachea. In total, 84,363 cells and 228,508 genes were included in the integrated analysis. A marker gene of SPTBN1 is highly expressed across all 15 organ types, particularly in the Fibroblasts, Smooth muscle cells, and Tissue stem cells of the Bladder, Esophagus, Heart, Muscle, Rectum, Skin, and Trachea. In contrast, EPDR1 is highly expressed in the Muscle, Heart, and Trachea, and PKDCC is only expressed in Heart. In conclusion, SPTBN1 is an essential protein gene in physiological development and plays a critical role in the high expression of fibroblasts in multiple organ types. Targeting SPTBN1 may prove beneficial for fracture healing and drug discovery. Author SummaryThree marker genes (SPTBN1, EPDR1, and PKDCC) are playing a critical role in the shared genetic mechanisms between bone and muscle. However, how these marker genes contribute to developing other tissues and organs at the cellular level is unknown. Here, we build on prior work to study an unappreciated degree of heterogeneity of three marker genes in 15 adult human organs by using single-cell RNA sequencing technology. Our analysis included 15 organ types: Bladder, Blood, Common Bile Duct, Esophagus, Heart, Liver, Lymph Node, Marrow, Muscle, Rectum, Skin, Small Intestine, Spleen, Stomach, and Trachea. In total, 84,363 cells from 15 different organ types were included. In all 15 organ types, SPTBN1 is highly expressed, including fibroblasts, smooth muscle cells, and skin stem cells of the bladder, esophagus, heart, muscles, and rectum. The first-time discovery of the high expression of SPTBN1 in 15 organ types suggests that it may play a critical role in physiological development. Our study concludes that targeting SPTBN1 may benefit fracture healing and drug discovery.