Biology subjects

Hansen, J. K.

Publications and source records attributed to Hansen, J. K..

6 recordsLinked to original sources

bioRxiv2025

Tumor-Derived Polyamines Initiate Fat Wasting in Cancer Cachexia

Cancer-associated cachexia (CC) is a fatal metabolic condition characterized by progressive loss of fat and muscle mass, yet its early molecular drivers remain poorly defined. Here, we identify a polyamine-dependent tumor-adipose crosstalk that triggers adipocyte lipolysis and fat wasting during the pre-cachexia stage, preceding systemic inflammation and muscle atrophy. Cancer-derived polyamines are enriched in extracellular vesicles and promote lipid mobilization via eIF5A hypusination, independent of adrenergic signaling. In preclinical models, polyamine accumulation associates with early fat loss and elevated circulating fatty acids. Clinically, automated CT imaging of newly diagnosed pancreatic cancer patients reveals increased adipose density, reflecting lipolysis, that correlates with circulating polyamine levels and predicts poor survival. These findings support polyamine metabolism as a mechanistic driver and candidate biomarker of early cachexia, providing a framework for early detection and targeted intervention.

cancer biology↗

bioRxiv2025

Genomic selection for accelerated heartwood formation in Pedunculate oak (Quercus robur L.) using whole-genome sequencing

Heartwood traits in trees are critical for timber quality but are notoriously difficult to phenotype due to their late expression and the need for destructive sampling. In this proof-of-concept study, we demonstrate that combining genome-wide association studies (GWAS) with Bayesian genomic prediction models provides an effective strategy to overcome these challenges. By using GWAS to preselect trait associated SNPs and integrating them into predictive models, we substantially improve the accuracy of genomic predictions for heartwood related traits in oaks. Our approach allows for reliable selection of superior genotypes at the seedling stage, long before heartwood traits can be directly measured, thus enabling early and cost-effective breeding decisions. We also identify the number of rings in sapwood as a genetically controlled, easily measured proxy trait that enhances selection strategies for heartwood content. Together, these findings provide a scalable framework for integrating genomics into operational tree breeding programs and demonstrate how combining GWAS and genomic prediction can accelerate the improvement of complex wood traits in long lived forest tree species.

genetics↗

bioRxiv2025

Genetic and plastic effects on trait variability in two major tree species: insights from common garden experiments across Europe

Phenotypic plasticity and genetic adaptation are key mechanisms that enable species to respond to changing environments. Tree traits do not vary independently but rather in coordination. However, our understanding of whether functional traits are governed by the same mechanism is far from complete. Thus, we aim at assessing the drivers of trait variability of sessile oak and European beech provenances across their distribution ranges. We estimated growth-related and leaf morphological traits from 9 and 11 provenances of oak and beech, respectively, grown in four different common gardens distributed across their respective distribution areas. Overall, phenotypic plasticity played a dominant role in explaining individual trait variability. For most oak traits, variation among provenances and genetically based plasticity were correlated with the climate of origin, whereas fewer significant associations were found for beech. In oak, climate-transfer distance analyses revealed that traits such as DBH, height, specific leaf area, and long-term growth responses to summer temperature decreased when provenances were moved away from their local precipitation regime. In beech, significant climate-transfer distances were fewer and primarily related to temperature-related parameters. These results suggest that natural selection and local adaptation may play a secondary but notable role. The pattern of multi-trait phenotypes indicates that resource-use strategies among provenances covary with the temperatures of origin in both species. The limited genetic responses in beech could hinder its survival if it reaches the boundaries of trait plasticity, while oak may better adjust through adaptation. Our study contributes to a better understanding of the interplay between genetic adaptation and phenotypic plasticity in long-lived forest trees.

ecology↗

bioRxiv2025

White and Brown Adipose Tissue Share a Common Fibro-Adipogenic Progenitor Population

Adipose tissue heterogeneity has emerged as a central factor in regulating adipose tissue function in physiology and pathophysiology, yet tools to model and study this diversity in vitro remain limited. Here, we performed single-cell RNA sequencing on cultured primary white and brown preadipocytes to assess how in vitro conditions impact progenitor identity. We identified two major subpopulations in both depots: committed adipogenic precursors (CAPs) and fibro-adipogenic progenitor-like cells (FAPLs). Remarkably, FAPLs were also present in brown adipose tissue, expanding the known landscape of progenitor populations in this depot. Trajectory and regulon analyses revealed that both white and brown FAPLs exhibit similar pro-fibrotic, stress-responsive signatures and diverge early from proliferating progenitor states. Integration of datasets showed that FAPLs from both depots cluster together, emphasizing their conserved identity, while CAPs remain depot-specific. Comparison to previously published in vivo single-cell datasets revealed that these in vitro populations, including brown adipose FAPLs, correspond to adipose-resident progenitor subtypes, validating the physiological relevance of this model for studying adipose tissue heterogeneity and development.

physiology↗

bioRxiv2024

Fecal microbial load is a major determinant of gut microbiome variation and a confounder for disease associations

The microbiota in individual habitats differ both in relative composition and absolute abundance. While sequencing approaches determine only the relative abundances of taxa and genes, experimental techniques for absolute abundance determination are rarely applied to large-scale microbiome studies. Here, we developed a machine learning approach to predict fecal microbial loads (microbial cells per gram) solely from relative abundance data. Applied to large-scale datasets (n = 34,539), we demonstrate that microbial load is the major determinant of gut microbiome variation and associated with numerous host factors. We found that for several diseases, the altered microbial load, not the disease itself, was the main driver of the gut microbiome changes. Adjusting for this effect substantially reduced the significance of more than half of the disease-associated species. Our analysis reveals that the fecal microbial load is a major confounder in microbiome studies, highlighting its importance for understanding microbiome variation in health and disease.

microbiology↗

bioRxiv2023

Heme biosynthesis regulates BCAA catabolism and thermogenesis in brown adipose tissue

With age, people tend to accumulate body fat and reduce energy expenditure1. Brown (BAT) and beige adipose tissue dissipate heat and increase energy expenditure via the activity of the uncoupling protein UCP1 and other thermogenic futile cycles2,3. The activity of brown and beige depots inversely correlates with BMI and age4-11, suggesting that promoting thermogenesis may be an effective approach for combating age-related metabolic disease12-15. Heme is an enzyme cofactor and signaling molecule that we recently showed to regulate BAT function16. Here, we show that heme biosynthesis is the primary contributor to intracellular heme levels in brown adipocytes. Inhibition of heme biosynthesis leads to mitochondrial dysfunction and reduction in UCP1. Although supplementing heme can restore mitochondrial function in heme-synthesis-deficient cells, the downregulation of UCP1 persists due to the accumulation of the heme precursors, particularly propionyl-CoA, which is a product of branched-chain amino acids (BCAA) catabolism. Cold exposure promotes BCAA uptake in BAT, and defects in BCAA catabolism in this tissue hinder thermogenesis17. However, BCAAs contribution to the TCA cycle in BAT and WAT never exceeds 2% of total TCA flux18. Our work offers a way to integrate current literature by describing heme biosynthesis as an important metabolic sink for BCAAs.

cell biology↗