bioRxiv Science⌕ Search

Biology subjects

Shoshkes Carmel, M.

Publications and source records attributed to Shoshkes Carmel, M..

3 recordsLinked to original sources

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↗

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↗

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↗