integrative-transcriptomic-analysis-obesity-associated-candidate

Integrative Transcriptomic Analysis of Obesity-Associated Candidate Genes in Pediatric Adipose Tissue

Tryptophan metabolism has been linked to pediatric obesity, although the transcriptomic evidence connecting obesity-associated genes with this pathway ...

Nanjing Medical University

Myasthenia gravis (MG) is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. The evidence suggests that the regulation of long noncoding RNAs (lncRNAs) that is mediated by transcription factors (TFs) plays a key role in the pathophysiology of MG. Nevertheless, the detailed molecular mechanisms of lncRNAs in MG remain largely undetermined.

FOSL1-mediated LINC01566 negatively regulates CD4 T-cell activation in myasthenia gravis.

Embryonal carcinoma (EC), characterized by a high degree of stemness similar to that of embryonic stem cells, is the most malignant subtype within non-seminomatous testicular germ cell tumors (TGCTs). However, the mechanisms underlying its malignancy remain unknown. In this study, we employed single-cell RNA sequencing to analyze four non-seminoma samples. Our differential expression analysis revealed high expression of SERPINB9 in metastatic EC cells. We conducted in vitro experiments to further investigate SERPINB9's role in the progression of EC. Functionally, the knockdown of SERPINB9 in NCCIT and NTERA-2 leads to a diminished migratory capability and decreased cis-platin resistance, as demonstrated by Transwell migration assay and drug sensitivity assay. Moreover, embryoid bodies showed reduced size and lower OCT4 expression, alongside heightened expression of differentiation markers AFP, ACTA2, and CD57 in shSERPINB9 cells. In vivo, the role of SERPINB9 in maintaining cancer stemness was validated by the limiting dilution assay. Mechanistically, Bulk RNA-seq further showed downregulation of ERK1/2 signaling and WNT signaling pathways with concomitant upregulation of differentiation pathways subsequent to SERPINB9 knockdown. Additionally, the analysis indicated increased levels of cytokines linked to tertiary lymphoid structures (TLS), such as IL6, IL11, IL15, CCL2, CCL5, and CXCL13 in shSERPINB9 cells, which were further validated by ELISA. Our research indicates that SERPINB9 plays a key role in driving tumor progression by enhancing tumor stemness and suppressing TLS. This study stands as the first to elucidate the molecular signature of non-seminomas at a single-cell level, presenting a wealth of promising targets with substantial potential for informing the development of future therapeutic interventions.

Single-cell landscape identified SERPINB9 as a key player contributing to stemness and metastasis in non-seminomas.

Seminoma is the most common solid malignant tumor of the testis in young males, significantly impacting fertility. Approximately 20% of seminomas metastasize, markedly increasing recurrence risk and compromising quality of life. To investigate the poorly understood mechanisms driving seminoma metastasis, we performed a comprehensive analysis by integrating single-cell RNA sequencing, TCGA data mining, and cell biology assays. We identified significant intratumoral heterogeneity. A subset of tumor cells expressing DPPA4 and PSMA7 showed high stemness, enhanced self-renewal, and association with metastasis. Knockdown of these genes reduced sphere formation, tumor migration and proliferation in Tcam-2 and NCCIT cells. Conversely, tumor cells overexpressing PAGE5 and SAT1 exhibited reduced stemness, migratory capacity and proliferation. In the immune microenvironment, we identified IFNG+ T cells, which recruit and activate other antitumor immune cells. These cells secrete IFN-γ, which promotes tumor differentiation, reduces stemness, and mitigates tumor aggressiveness. Based on these findings, we further developed a molecular panel to aid in the identification of seminomas with a higher risk of metastasis. In conclusion, our study identifies unique molecular signatures that facilitate risk stratification based on metastatic potential, providing valuable insights for improving precision medicine.

Article	Year
FOSL1-mediated LINC01566 negatively regulates CD4 T-cell activation in myasthenia gravis. Journal of neuroinflammation\| PubMed ID: 39113081	2024
Single-cell landscape identified SERPINB9 as a key player contributing to stemness and metastasis in non-seminomas. Cell death & disease\| PubMed ID: 39528470	2024
Single-cell analysis unravels divergent gene signatures shaping seminoma stemness and metastasis. Cell death discovery\| PubMed ID: 41203637	2025

Biying Chen

Biography

JoVE Journal Publications

Other Publications