Soares, K. | bioRxiv Science

bioRxiv2025

Environment and weight class linked to skin microbiome structure of juvenile Eastern hellbenders (Cryptobranchus alleganiensis alleganiensis) in human care

Amphibian skin is integral to promoting normal physiological processes in the body and promotes both innate and adaptive immunity against pathogens. The amphibian skin microbiota is comprised of a complex assemblage of microbes and is shaped by internal host characteristics and external influences. Skin disease is a significant source of morbidity and mortality in amphibians, and increasing research has shown that the amphibian skin microbiota is an important component in host health. The Eastern hellbender (Cryptobranchus alleganiensis alleganiensis) is a giant salamander declining in many parts of its range, and captive-rearing programs are important to hellbender recovery efforts. Survival rates of juvenile hellbenders in captive-rearing programs are highly variable, and mortality rates are overall poorly understood. Deceased juvenile hellbenders often present with low body condition and skin abnormalities. To investigate potential links between the skin microbiota and body condition, we collected skin swab samples from 116 juvenile hellbenders and water samples from two holding tanks in a captive-rearing program. We used 16s rRNA gene sequencing to characterize the skin and water microbiota and observed significant differences in the skin microbiota by weight class and tank. The skin microbiota of hellbenders that were housed in tanks in close proximity were generally more similar than those housed physically distant. A single taxa, Parcubacteria, was differentially abundant by weight class only and observed in higher abundance in low weight hellbenders. These results suggest a true association between this taxa and Low weight hellbenders. Additional research is needed to investigate how husbandry factors and potential pathogenic organisms, such as Parcubacteria, impact the skin microbiota of hellbenders and ultimately morbidity and mortality in the species.

microbiology↗

bioRxiv2023

Progressive plasticity during colorectal cancer metastasis

Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5+ intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.

cancer biology↗