Biology subjects

Labrosse, M.

Publications and source records attributed to Labrosse, M..

2 recordsLinked to original sources

bioRxiv2026

Human Lymph Node Cellular Senescence Atlas Reveals Age-Dependent Alteration in Germinal Center B Cell Function and Niches

Immunosenescence, the age-associated decline in immune function, is a key feature of human aging. In human lymphoid organs, however, the specific immune cell populations that acquire senescence-associated phenotypes during aging and how they influence the surrounding tissue microenvironment remain poorly understood. A spatially resolved map of these senescence-associated immune states in human lymphoid tissues could help clarify their relationship with aging and their potential contributions to the progressive decline of immune function. Here, we integrated single-cell and spatial multi-omics to systematically characterize age-related senescence in human lymph nodes (LNs). Single-cell transcriptomics of lymphoid tissues from donors aged 18 to 100 years old identified 34 immune and stromal cell types and revealed age-associated upregulation of senescence signatures in specific populations. Spatial proteomic profiling of 99 LN sections from 51 donors (18-86 years) using high-plex immunofluorescence ([~]20 million cells) mapped senescence markers (p16, p21, HMGB1, -H2AX) at single-cell resolution, revealing diverse senescent-like cell types ("senotypes") and a stepwise shift from extrafollicular to germinal center (GC) localization with age. Notably, we observed focal clonal-like senescence in GC B cells in older donor LNs. Spatial transcriptomics, epigenomics, and metabolic imaging of selected samples further elucidate the multi-omics signatures and underlying mechanisms of functional impairment, metabolic remodeling, and distinct regulatory programs in senescent-like GC B cells. This study presents a comprehensive spatial atlas of senescence-associated immune states in human lymph nodes, revealing cell-type-specific and spatial heterogeneity that may contribute to immunosenescence and the decline of immune function during aging.

immunology↗

bioRxiv2025

Mobilizable adipose stromal cells fuel regenerative adipogenesis in injured muscle

Skeletal muscle regeneration is a highly orchestrated process involving the dynamic interplay of multiple cell types. Among these, fibro-adipogenic progenitors (FAPs), a population of resident mesenchymal stromal cells (MSCs), are essential for creating a supportive microenvironment that promotes satellite cell differentiation and modulates immune responses. Our recent work revealed that adipose stromal cells (ASCs) from subcutaneous adipose tissue (ScAT) infiltrate the injured muscle within the first 24h post-injury, contributing significantly to the regenerative process. Consequently, the FAP population in the regenerating muscle comprises both resident FAPs and infiltrated ASCs. In the present study, using single cell RNA-seq in a mouse model with trackable KikGR+ ASCs and bioinformatics analyses, we identify Limch1+/Prg4+ ASCs as the primary Mobilizable ASCs (Mob-ASCs) that migrate to and infiltrate the injury site. Notably, this migration is detectable as early as 14 hours post-injury. We demonstrate that these cells are pre-activated within the ScAT, primed to initiate both migratory and regenerative programs. Intriguingly, bioinformatic inference of key activated transcription factors suggested that adipogenesis is also activated in these cells. Leveraging supervised machine learning, we tracked the fate of Mob-ASCs within the regenerating muscle post-injury, where they continue to execute these programs. Importantly, these cells lineage is cued towards a fate of adipogenesis. In vivo, we observed transient generation of adipocytes with a peak at 7-9 days post-injury to which infiltrated ASCs contributed. In vitro, conditioned media assays further revealed that adipocytes derived from ASCs--but not those from FAPs--enhance myoblasts fusion. Collectively, our findings establish Limch1+/Prg4+ ASCs as the Mobilizable ASC population and suggest that their transient adipogenic differentiation is beneficial for muscle regeneration.

physiology↗