Biology subjects

Canella, M.

Publications and source records attributed to Canella, M..

5 recordsLinked to original sources

bioRxiv2026

Epithelial MHC II antigen presentation dynamically informs intestinal homeostasis and injury

The intestinal epithelium plays a pivotal role in balancing immune tolerance and inflammation, yet how it communicates tissue state to the adaptive immune system remains unclear. Here, we show that intestinal epithelial cells (IECs) encode tissue identity and injury into the major histocompatibility complex class II (MHC II) ligandome. We employed integrated single cell transcriptomics, quantitative proteomics, and high-depth in vivo immunopeptidomics to map the MHC class II self-peptidome of the mouse small intestine across epithelial and immune compartments. Mature enterocytes and intestinal stem cells (ISCs) emerged as the dominant epithelial antigen-presenting cells (APCs), displaying a compartmentalized repertoire of endogenous self-immunopeptides reflecting epithelial differentiation and function. Disruption of epithelial MHC II expression led to loss of antigenic compartmentalization, immune infiltration, extracellular matrix remodeling, and emergence of inflammation-associated immune ligands, demonstrating that epithelial MHC II is required to maintain homeostasis. Functionally, a subset of ISC-derived self-immunopeptides preferentially promotes regulatory CD4{square} T cell responses, linking epithelial antigen presentation and peripheral tolerance. During gut inflammation, the epithelial MHC II landscape shifted toward damage-associated antigens. Together, these findings establish epithelial MHC II presentation as a context-dependent tissue-immune communication system that promotes tolerance in homeostasis and alerts to tissue injury during inflammation.

immunology↗

bioRxiv2025

Transcriptome profiles of telocytes along the intestinal crypt-villus axis

Background & aimsIntestinal epithelial cells rely on a complex array of signals from the stromal microenvironment to determine their fate and function along the crypt-villus axis, but the precise cellular sources and combinations of signals regulating each position remain poorly defined. MethodsHere, we present a high-resolution atlas of a unique mesenchymal cell type previously identified as telocytes, mapped along the crypt-villus axis using single-cell RNA sequencing integrated with in-situ approaches and reporter mouse models. ResultsWe identify four spatially distinct telocyte subtypes: crypt, villus base, villus mid and villus tip, each with a unique gene expression profile. Crypt telocytes are enriched for canonical Wnt signaling components that support stem and progenitor cell maintenance, while villus base telocytes are a source of Bmps (bone morphogenic proteins) and express contractility-associated genes, suggesting a role in tissue architecture. Villus mid telocytes display signatures of immune regulation and inflammation, while villus tip telocytes are specialized for the regulation of ribonucleoprotein complexes and nutrient sensing. ConclusionsThis atlas provides a foundational resource for understanding how diverse telocyte populations coordinate signaling environments and shape intestinal homeostasis through both epithelial interactions and extensive crosstalk among themselves.

cell biology↗

bioRxiv2024

Immortalized Intestinal Telocytes - A Stem Cell Niche In Vitro

Telocytes, a distinct type of mesenchymal cell, have recently emerged as crucial components of the intestinal stem cell niche, primarily by providing essential Wnt proteins that drive stem cell function. However, their detailed biology and the specific mechanisms by which they regulate stem cell activity remain largely unexplored. Here, we established an immortalized intestinal telocyte cell line that retains the key cellular and molecular characteristics of native telocytes. Remarkably, this cell line, unlike telocyte-depleted immortalized mesenchyme, supports the growth of both mouse and human organoids in co-culture without the need for external factor supplementation. These findings indicate that telocytes are not only essential but are also sufficient to maintain stem cell activity. This immortalized telocyte line provides a valuable source of factors that support stem cell activity in vitro, offering a powerful tool for advancing our understanding of telocyte biology and the reciprocal communication between stem cells and their niche.

cell biology↗

bioRxiv2023

Telocytes are a critical source of Wnts essential for hair follicle regeneration

Self-renewing tissues rely on stem cells (SCs) to regenerate differentiated cells, requiring precise coordination between SCs and their progeny. Here, we investigated how SC activity is regulated across multiple epithelial layers, using the hair follicle (HF) as a model system. We uncovered an extensive, interconnected network of telocytes, specialized mesenchymal cells, that spans all HF layers, including regions previously thought to lack mesenchymal or connective tissue components. These telocyte networks remain in constant contact with SCs and their progeny throughout regeneration, dynamically adapting their structure and molecular profile to provide localized, phase-specific signals. By employing two independent mouse models to ablate telocytes or disrupt their Wnt signaling, we demonstrate that telocyte networks are an essential component of the SC niche. Our findings propose a revised, integrative model of the SC niche, in which telocyte networks and their Wnt production play a central role in adult SC biology and tissue regeneration.

cell biology↗

bioRxiv2020

A fully defined pluripotent stem cell derived multi-liver-cell model for steatohepatitis and fibrosis

Chronic liver injury, as observed in non-alcoholic steatohepatitis (NASH), progressive fibrosis, and cirrhosis, remains poorly treatable. Steatohepatitis causes hepatocyte loss in part by a direct lipotoxic insult, which is amplified by derangements in the non-parenchymal cellular (NPC) interactive network wherein hepatocytes reside, including, hepatic stellate cells, liver sinusoidal endothelial cells and liver macrophages. To create an in vitro culture model encompassing all these cells that allows studying liver steatosis, inflammation and fibrosis caused by NASH, we here developed a fully defined hydrogel microenvironment, termed hepatocyte maturation (HepMat) gel, that supports maturation and maintenance of pluripotent stem cell (PSC)-derived hepatocyte- and NPC-like cells for at least one month. The HepMat-based co-culture system modeled key molecular and functional features of TGF{beta}-induced liver fibrosis and fatty-acid induced inflammation and fibrosis better than monocultures its constituent cell populations. The novel co-culture system should open new avenues for studying mechanisms underlying liver steatosis, inflammation and fibrosis as well as for assessing drugs counteracting these effects.

bioengineering↗