Single-cell transcriptomic analysis reveals age-related remodeling of brain endothelial cells.

Endometriosis (EMS) is a prevalent gynecological disorder classified as an estrogen-dependent disease and characterized by the presence of normal endometrial tissue outside the uterine cavity, severely affecting women’s physical and mental well-being. Common sites for ectopic endometrial tissues include the ovaries, sacro-ligament, rectouterine pouch, pelvic peritoneum, as well as the rectum, bladder, and nerves. Approximately 10% of women of reproductive age are affected by EMS. Patients may experience complications such as infertility, chronic pelvic pain, and dysmenorrhea, with varying clinical manifestations depending on the ectopic locations of the endometrial tissue. For example, EMS involving the ovaries can lead to the formation of ovarian cysts, which may rupture and result in acute gynecological abdominal symptoms. When EMS affects the sacro-ligament and rectouterine pouch, patients may experience dyspareunia, as well as palpable nodules in the sacro-ligament and tenderness in the rectouterine pouch., Endometrial tissue located in the rectum can lead to intestinal masses, resulting in symptoms such as intestinal perforation. When nerves are involved, localized pain may manifest., Currently, laparoscopy remains the gold standard for diagnosing EMS; however, it is invasive, costly, and operator-dependent, making it difficult to use for large-scale screening and early diagnosis. Treatment strategies typically involve surgical intervention and conservative pharmacological management. Unfortunately, approximately half of patients experience recurrence within five years post-treatment, coupled with a potential risk for malignant transformation into ovarian endometrioid adenocarcinoma., Therefore, exploring non-invasive or minimally invasive biomarkers associated with EMS is crucial for early diagnosis, enhancing the understanding of its etiology, and refining treatment strategies, highlighting the urgent need for developing reliable biomarkers in the near future. Small ubiquitin-related modifier (SUMO)ylation is a post-translational modification that serves as a crucial molecular regulatory mechanism in cell death processes, including apoptosis, autophagy, and senescence. It has been shown that SUMOylation can stabilize the transcription factor (TF) 21. The SUMOylation of TF21 may enhance its interaction with upstream stimulatory factor 2, thereby increasing the binding ability of upstream stimulatory factor 2 with the SF-1 and estrogen receptor beta promoters and influencing the proliferation of embryonic stem cells, which contributes to the development of EMS. However, research on SUMOylation in the context of EMS remains limited, and its mechanisms are not yet fully understood. The causal relationship between key SUMOylation-related genes (SRGs) and EMS remains unclear. Moreover, the roles of key SRGs in this condition remain unclear. This study primarily utilizes single-cell RNA sequencing (scRNA-seq) data and conventional transcriptomic data, employing various bioinformatics approaches, including Mendelian randomization (MR) analysis, differential expression analysis, and weighted gene co-expression network analysis (WGCNA), to identify SUMOylation-related biomarkers in EMS. Additionally, gene set enrichment analysis (GSEA) was performed on these biomarkers, and a long non-coding RNA (lncRNA)-microRNA (miRNA)-biomarker networks and TF-biomarker-miRNA networks were constructed. Immune infiltration analysis was conducted to assess the levels of immune cell infiltration in EMS. Furthermore, pseudo-time analysis and cell communication analysis were based on identified key cell types to elucidate their significance in EMS. Our findings may provide new insights for the diagnosis and treatment of patients with EMS.