bims-raghud Biomed News
on RagGTPases in human diseases
Issue of 2025–06–22
three papers selected by
Irene Sambri, TIGEM



  1. Kidney360. 2025 Jun 19.
      Tuberous sclerosis complex (TSC) is a highly variable autosomal dominant disease characterized by dysregulated organ development and growth. Benign tumors, termed hamartomas, may occur across organ systems but typically involve the kidney, brain, skin, heart, and lung. The diagnosis, surveillance, and clinical management of TSC requires a multidisciplinary approach, adopted by dedicated multispecialty centers worldwide. Nephrology involvement predominantly stems from the morbidity and mortality related to the prototypical kidney lesion, angiomyolipomas, whose presence and degree confers risk for chronic kidney disease, hypertension, retroperitoneal bleeding, and possibly renal cell carcinoma. Surveillance of kidney structural lesions, kidney function, and blood pressure may enable early interventions that limit kidney-related morbidity and mortality, such as mTOR inhibitor therapy. Here we review the epidemiology, genetics, and pathogenesis of TSC, and how these inform the evaluation, diagnosis, and clinical management of TSC from the vantage point of the treating nephrologist.
    DOI:  https://doi.org/10.34067/KID.0000000904
  2. Nat Commun. 2025 Jun 20. 16(1): 5309
      The ureter is the outlet for urine produced by the kidney. Recent advances in stem cell biology have enabled the in vitro generation of kidney organoids from pluripotent stem cells (PSCs), but they lack the ureter, which hinders the smooth drainage of urine. By mimicking the in vivo developmental process of ureteral stromal progenitors (SPs) from the posterior intermediate mesoderm, we report here in vitro induction protocols for ureteral SPs from mouse and human PSCs. When the induced SPs were combined with ureteral epithelia derived from mouse embryos, the elongated, multilayered ureteral structure was reconstituted, exhibiting peristaltic constriction. Some of the pathological features associated with the loss of Tbx18/TBX18 in mice and humans can be modeled using induced SPs lacking functional TBX18. Furthermore, the ureter-like spherical organoids entirely derived from mouse and human PSCs can also be generated by combining the induced SPs and the epithelial progenitor, the ureteric bud. Therefore, our induction protocols for ureteral SPs will be useful for the elucidation of ureteral development and diseases, and will be an important step towards functional kidney organoids with urine flow.
    DOI:  https://doi.org/10.1038/s41467-025-60693-6
  3. EMBO Rep. 2025 Jun 17.
      Melanoma exhibits high intratumoral heterogeneity, characterized by a diverse population of cells undergoing dynamic transitions between cellular states. These adaptive changes enable melanoma cells to survive in the harsh tumor microenvironment, acquire drug resistance, and metastasize. One such state, quiescence, has been linked to both relapse and drug resistance, but its underlying biology and molecular mechanisms remain poorly understood. Our study challenges the conventional understanding of melanoma quiescence. Contrary to the notion of a rare, unique subpopulation, we demonstrate that quiescence is a highly dynamic state accessible to most, if not all, melanoma cells. This state is exquisitely sensitive to microenvironmental cues. We identify GPNMB as a marker of quiescence, that is expressed in both primary and metastatic tumors. GPNMB-positive cells exhibit a pro-metastatic phenotype and are enriched in metastatic sites, suggesting a potential role for quiescence in tumor dissemination. Our findings position GPNMB as a valuable marker for isolating quiescent melanoma cells and as a potential therapeutic target to tackle metastasis.
    Keywords:  Hypoxia; Melanoma; Metastasis; Quiescence; Target Therapy
    DOI:  https://doi.org/10.1038/s44319-025-00501-w