Pd16-10 Mitochondrial Dysfunction in Wilms Tumor Cancer Stem Cells

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (PD16)1 May 2024PD16-10 MITOCHONDRIAL DYSFUNCTION IN WILMS TUMOR CANCER STEM CELLS Osanna Kosoyan, Sargis Sedrakyan, Stefano Da Sacco, and Laura Perin Osanna KosoyanOsanna Kosoyan , Sargis SedrakyanSargis Sedrakyan , Stefano Da SaccoStefano Da Sacco , and Laura PerinLaura Perin View All Author Informationhttps://doi.org/10.1097/01.JU.0001009560.23593.56.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We have identified in cells co-expressing SIX2 and CITED1 the cancer stem cells (CSC) that regulate Wilms tumor (WT) development. Our comparative in vitro and in vivo analysis highlighted that mitochondrial dysregulation plays a critical role in modulating biology of these CSC. In this work, we have performed transcriptomics analysis and mechanistic in vitro studies to assess impact of mitochondria function on WT stem cell biology. METHODS: SIX2+CITED1+ expressing CSC were isolated using smartflare probes from favorable and unfavorable WT and human fetal kidney (hFK) samples and processed for bulk and scRNA-seq. Differential gene expression and GO ontology analysis were performed to identify differences across samples. Data generated were further confirmed by bulk RNAseq on WT-CSC in which SIX2 or CITED1 were either knocked down or overexpressed, by Spatial Transcriptomics analysis, as well as by in vitro experiments and in vivo WT xenografts. RESULTS: scRNAseq analysis revealed key differences in gene expression involved in mitochondrial function and dynamics including fission (DRAP1, DNM2, MFF and MEIF2) and fusion (MFN1/2 and OPA1) along with changes in the normal metabolomic and oxidative state. In addition, knocking down SIX2 or CITED1 in WT-NP confirmed their critical role in regulating mitochondrial dynamics and influencing their proliferative capacity and self-renewal. Spatial transcriptomics analysis further confirmed our findings, indicating the presence of mitochondrial and metabolic dysregulation in WT-CSC. CONCLUSIONS: These data for the first time identify mitochondrial changes as a possible driver in regulating WT formation and progression, in addition to offering potential target for the discover of new WT treatments. Source of Funding: Gofarr Kidney Fund Pablove © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e369 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Osanna Kosoyan More articles by this author Sargis Sedrakyan More articles by this author Stefano Da Sacco More articles by this author Laura Perin More articles by this author Expand All Advertisement PDF downloadLoading ...