bioRxiv Science⌕ Search

bioRxiv · 10.64898/2026.01.28.702281

Declining muscle hyperplasia in juvenile trout is driven by rapid limitation of muscle stem cell capacity and niche functionality

Abstract

Unlike mammals and birds, where new muscle fiber formation (hyperplasia) ceases around birth, large and fast-growing fish such as rainbow trout undergo a spectacular post-hatching surge of hyperplasia, followed by a considerably delayed hyperplasia decline. This study investigated the roles of the satellite cells (SCs) and their niche in this decline by determining the number and the myogenic capacity of the muscle progenitors as well as the functionality of their direct tissue environment. Histological analysis revealed a significant decrease in hyperplasia (fibers <25 {micro}m) and SC numbers (Pax7+) between 10 g and 500 g trout. Transplantation experiments using muscle-derived cells (MDCs) from mlc2-GFP transgenic trout (10 g to 2 kg donors into 10 g to 2 kg recipients) demonstrated a marked decline in both intrinsic myogenic capacity and niche functionality as trout grow from 10 g to 500 g. Detailed analyses of GFP+ fibers produced after transplantation showed an enrichment of small-diameter GFP+ fibers in 10 g but not 100 g trout recipient muscles, showing a rapid impairment in niche ability to support hyperplasia. In addition, transplantation of MDCs from trout of different ages but the same weight, showed that increasing trout weight, but not aging, is associated with an impairment of the myogenic capacity of progenitors and their niche. Overall, these findings show that the muscle hyperplasia decline in trout is primarily driven by early impairment of the SC niche, followed by a reduction in their myogenic capacity and number, with weight gain playing a more critical role than aging.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Jagot, S., Sabin, N., Ralliere, C., Branthonne, A., Chesnais, M., Duret, C., Bugeon, J., Rescan, P.-Y., Rouger, K., Gabillard, J.-C.. 2026-01-31. Declining muscle hyperplasia in juvenile trout is driven by rapid limitation of muscle stem cell capacity and niche functionality. https://doi.org/10.64898/2026.01.28.702281

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Nucleosome Core Allostery Governs Chromatin Recognition and Cell Fate

Nucleosomes regulate chromatin folding, accessibility, and factor recruitment. Current models primarily attribute these functions to histone tail modifications, while the core is largely viewed as a structural scaffold. Yet subtle changes within the nucleosome core can produce profound functional consequences, and the mechanisms underlying these effects remain unclear. Here, we describe nucleosome core allostery as a fundamental principle of chromatin regulation that amplifies the impact of minimal nucleosome variations. Leveraging natural differences between H2A.Z variants, we show that the nucleosome core encodes distinct conformational dynamics that propagate allosterically, thereby controlling nucleosome accessibility and recognition by chromatin factors. As a result, a single buried amino acid substitution alone is sufficient to reprogram nucleosome dynamics and bias cell identity. Our findings establish the nucleosome core as an allosteric regulatory module and provide a generalizable framework for how subtle variation within nucleosomes is amplified into diverse biological outcomes in development and disease.

cell biology↗

SOX4 Reprograms Adipose Stromal Cells into a Cancer-Associated Fibroblast-like State to Drive Metabolic Disease

Pathogenic adipose tissue remodeling promotes metabolic disease in obesity, but the mechanisms that establish this unhealthy tissue state remain poorly understood. Here, we show that obesity drives SOX4-dependent reprogramming of mesenchymal stromal cells (MSCs) into cancer-associated fibroblast-like (CAF-like) cells that promote adipose tissue dysfunction. TGF{beta} signaling is elevated in obesity and activates SOX4 in mouse and human MSCs, inducing their conversion to a CAF-like state. In mice, MSC-specific SOX4 activation induces the CAF-like program and exacerbates adipose tissue inflammation and glucose intolerance, whereas Sox4 deletion attenuates inflammation and improves glucose homeostasis during obesity. We further identify the growth factor Midkine (MDK) as a SOX4-regulated paracrine effector produced by CAF-like cells. MDK inhibition in obese mice reduces adipose tissue inflammation and improves metabolic function. Together, these findings define a TGF{beta}-SOX4-MDK stromal signaling axis that drives pathological adipose tissue remodeling in obesity and highlight this pathway as a potential therapeutic target for improving metabolic health.

cell biology↗

PDLIM5 Modulates YAP1 Localisation and Fibrogenic Gene Expression in Hepatic Stellate Cells

Hepatic stellate cells (HSCs) are the key cellular drivers of liver fibrosis. During liver injury and chronic inflammation HSCs adopt an activated phenotype and secrete fibrotic extracellular matrix (ECM) components such as collagen 1. Mechanical cues derived from the fibrotic ECM drive and support the activation of HSCs, via mechanisms that involve integrins and the mechano-sensitive transcriptional regulator YAP1. It is not yet well understood how external mechanical cues are translated into a molecular response that alters YAP1 nuclear shuttling. There is evidence that suggests the PDZ and LIM domain protein (PDLIM) 5 can regulate YAP1 shuttling in human epithelial cells. We therefore investigated whether PDLIM5 is expressed in HSCs and contributes to YAP1 associated HSC mechano-activation. PDLIM5 protein was detected in HSCs in fibrotic human and mouse liver. PDLIM5 transcript and protein were expressed by primary human and mouse HSCs and by the immortalised HSC LX-2 cell line. PDLIM5 localised with actin stress fibres suggesting a role in HSC adhesion. Co-immunoprecipitation and proximity ligation in LX-2 cells support an association between PDLIM5 and YAP1. We used pharmacological (paclitaxel) and genetic (siRNA and CRISPRi) approaches to inhibit PDLIM5 in HSCs. Inhibiting PDLIM5 reduced YAP1 nuclear localisation and fibrotic gene (COL1A1, ACTA2) expression in LX-2 cells. Overall, these data support a role for PDLIM5 in regulating YAP1 localisation and fibrogenic gene expression in HSCs.

cell biology↗