Biology subjects

Fergatova, A.

Publications and source records attributed to Fergatova, A..

2 recordsLinked to original sources

bioRxiv2026

A blastema in sea star larvae integrates wound signaling to drive regeneration-specific and developmental gene expression patterns.

Whether regeneration depends on the reactivation of developmental programs, regeneration-specific regulatory mechanisms, or both remains a central question in regeneration biology. Here, we investigate these processes in regenerating larvae of the sea star Patiria miniata, a deuterostome with robust regenerative capacity. By integrating single-nucleus transcriptomics with chromatin accessibility profiling across development and regeneration, we identify a regeneration-induced blastema cell state that is molecularly distinct from pre-existing larval populations and serves as the source of regenerated tissues. We show that regeneration is associated with distinct classes of regeneration-responsive enhancers, including regeneration-specific elements and enhancers reused from development, which link wounding signals to gene regulatory network (GRN) activation. These enhancer classes converge on regulatory programs associated with the transcription factor Runx, positioning Runx as a central node within the inferred regeneration GRN. Notably, we identify a Runx-associated regulatory framework that provides a mechanistic explanation for the de novo emergence of sox4 cells during regeneration through novel deployment of developmentally shared enhancers. Together, our results provide a framework for how wound-induced signals specify regenerative cell states and how regeneration-specific and developmental gene regulatory networks may be coordinated to rebuild lost tissues.

developmental biology↗

bioRxiv2026

Mitochondrial Oxygen Consumption Drives Lung Tumor Hypoxia and Resistance to Therapy via Copy Number Alteration in Mitochondrial Electron Transport Subunit NDUFB5

Decades of research have shown that tumor hypoxia is associated with resistance to anti-cancer treatments. Analysis of TCGA gene expression profiles indicates that NSCLC is among the most hypoxic of cancers despite the high levels of oxygen in the surrounding lung tissue. Several groups have shown that extrinsic factors such as poorly formed tumor vascular contributes to tumor hypoxia. Here, we have investigated the possibility that genetic abnormalities within the tumor also contribute to the development of hypoxia. Our analysis of NSCLC patient datasets in the Cancer Genome Atlas (TCGA) PanCancer and ORIEN datasets revealed a strong correlation between tumor hypoxia and amplification of chromosome 3q which is found in up to 40% of NSCLC. Several oncogenic driver genes have been identified in 3q, and we identified a passenger gene encoding mitochondrial complex I subunit NDUFB5 at 3q26.33. To provide experimental evidence that NDUFB5 amplification can drive tumor hypoxia, we have used CRISPR activation technology to generate murine cells overexpressing the endogenous NDUFB5 gene. We found that cells overexpressing NDUFB5 have elevated rates of oxygen consumption, and tumors grown from these cells have increased amounts of hypoxia with associated treatment resistance. Here, we investigate the impact of manipulating NDUFB5 gene expression on mitochondrial complex I activity and experimentally validate the clinical observations that NDUFB5 overexpression leads to increased levels of intratumoral hypoxia and increased resistance to radiation therapy and immunotherapy.

cancer biology↗