Single-Cell RNAseq Resolve the Potential Effects of LanCL1 Gene in the Mouse Testis

Infertility affects lots of couples, half of which are caused by male factors. The LanCL1 gene is highly expressed in testis specifically, which might affect the development of sperms. In order to understand the potential functions of the LanCL1 gene in the testis, this study was conducted with constructed transgenic LanCL1 knockout mice. The mouse breeding experiment, semen analysis and single-cell RNAseq of testicular tissue were performed. Results suggested that the LanCL1 gene would significantly influence the reproduction ability and sperm motility of male mice. Single-cell RNAseq also confirmed the high expression of the LanCL1 gene in the spermatocytes and spermatids. Downregulating the LanCL1 gene expression could promote M2 macrophage polarity to maintain testicular homeostasis. Moreover, the LanCL1 gene could affect both the germ cells and stromal cells through various pathways such as the P53 signaling and the PPAR signaling pathway to disturb the normal process of spermatogenesis. However, no effects of the LanCL1 gene in testosterone synthesis and serum testosterone level were shown. Further studies are needed to discuss the mechanisms of the LanCL1 gene in the various cells of the testis independently

CircSorbs1 regulates myocardial regeneration and reduces cancer therapy-related cardiovascular toxicity through the Mir-99/GATA4 pathway

Abstract Due to the cancer therapy-related cardiovascular toxicity, heart failure following cancer therapy has a significant mortality rate. Gene-targeted therapy promotes the re-entry of existing cardiomyocytes into the cell cycle to achieve myocardial regeneration, which is a promising strategy for preventing and treating heart failure after myocardial infarction. Circular RNAs (circRNAs) are considered as potential targets for myocardial regeneration due to their strong stability, resistance to degradation, and potential role in heart development and cardiovascular diseases. By comparing the myocardial tissue of mice in the sham operation group and the Doxorubicin therapy group (DOX), we observed a significant decrease in Cirsorbs expression in the DOX group. Cirsorbs was predominantly localized in cardiomyocytes and exhibited high conservation. Subsequent investigations revealed that Cirsorbs could promote myocardial proliferation and inhibit myocardial apoptosis. Mechanistic studies further demonstrated that Cirsorbs could bind to miR99 and reduce its expression level. Meanwhile, miR99 was found to bind to GATA4 mRNA and decrease its expression level. The binding of Cirsorbs to miR99 alleviated the repression of miR99, thereby enhancing GATA4 expression and the transcription of downstream cyclin A2 and cyclin E1. This, in turn, increased cardiomyocyte proliferation and reduced apoptosis. In conclusion, Cirsorbs holds promise as an effective target for myocardial regeneration in reducing cancer therapy-related cardiovascular toxicity

Metabolic heterogeneity in clear cell renal cell carcinoma revealed by single-cell RNA sequencing and spatial transcriptomics

Abstract Background Clear cell renal cell carcinoma is a prototypical tumor characterized by metabolic reprogramming, which extends beyond tumor cells to encompass diverse cell types within the tumor microenvironment. Nonetheless, current research on metabolic reprogramming in renal cell carcinoma mostly focuses on either tumor cells alone or conducts analyses of all cells within the tumor microenvironment as a mixture, thereby failing to precisely identify metabolic changes in different cell types within the tumor microenvironment. Methods Gathering 9 major single-cell RNA sequencing databases of clear cell renal cell carcinoma, encompassing 195 samples. Spatial transcriptomics data were selected to conduct metabolic activity analysis with spatial localization. Developing scMet program to convert RNA-seq data into scRNA-seq data for downstream analysis. Results Diverse cellular entities within the tumor microenvironment exhibit distinct infiltration preferences across varying histological grades and tissue origins. Higher-grade tumors manifest pronounced immunosuppressive traits. The identification of tumor cells in the RNA splicing state reveals an association between the enrichment of this particular cellular population and an unfavorable prognostic outcome. The energy metabolism of CD8+ T cells is pivotal not only for their cytotoxic effector functions but also as a marker of impending cellular exhaustion. Sphingolipid metabolism evinces a correlation with diverse macrophage-specific traits, particularly M2 polarization. The tumor epicenter is characterized by heightened metabolic activity, prominently marked by elevated tricarboxylic acid cycle and glycolysis while the pericapsular milieu showcases a conspicuous enrichment of attributes associated with vasculogenesis, inflammatory responses, and epithelial–mesenchymal transition. The scMet facilitates the transformation of RNA sequencing datasets sourced from TCGA into scRNA sequencing data, maintaining a substantial degree of correlation. Conclusions The tumor microenvironment of clear cell renal cell carcinoma demonstrates significant metabolic heterogeneity across various cell types and spatial dimensions. scMet exhibits a notable capability to transform RNA sequencing data into scRNA sequencing data with a high degree of correlation