BackgroundTumor heterogeneity is the key driver of disease progression and therapeutic resistance in clear cell renal cell carcinoma (ccRCC). Within this landscape, mitochondrial (MT) heterogeneity has emerged as a critical but poorly understood feature.
This study identified a specific manifestation of MT heterogeneity termed “nucleo-mitochondrial expression asymmetry (NMA)”. It is characterized by a dysregulated burst of mitochondrial DNA (mtDNA)-encoded genes compared to the nuclear genome, marking a pivotal tipping point in tumor proliferation and spatial reconstruction.MethodsWe employed an integrative multi-omics approach combining single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (stRNA-seq), and mass spectrometry imaging (MSI)-based spatial metabolomics from the Tongji Renal Cell Carcinoma (TJ-RCC) cohort.
To identify and characterize the profound NMA malignant subpopulations, we utilized Gaussian Mixture Model (GMM) clustering, CytoTRACE 2 for differentiation potential, and scFEA for metabolic flux inference. We implemented neighborhood and pseudo-spatiotemporal map (pSM) analyses to quantify spatial reconstruction.
Frontiers in Immunology published a clinical update in Infectious Disease on 12 Jun 2026.
The item focuses on Nucleo-mitochondrial asymmetry profiles the proliferative engine and spatial niche reconstruction in clear cell renal cell carcinoma.
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