Biology subjects

Ben-Porath, I.

Publications and source records attributed to Ben-Porath, I..

3 recordsLinked to original sources

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↗

bioRxiv2021

Mapping cellular subpopulations within triple negative breast cancer tumors provides a tool for cancer sensitization to radiotherapy

Triple negative breast cancer (TNBC) is an aggressive type of cancer that is known to be resistant to radiotherapy (RT). Evidence is accumulating that is indicative of the plasticity of TNBC, where one cancer subtype switches to another in response to various treatments, including RT. In this study we aim to overcome tumor resistance by designing TNBC-sensitizing targeted therapies that exploit the plasticity occurring due to radiation exposure. Using single cell analysis of molecular changes occurring in irradiated TNBC tumors, we identified two initially undetected distinct subpopulations, represented by overexpressed Her2 and cMet, expanding post-RT and persisting in surviving tumors. Using murine cancer models and patient-derived TNBC tumors, we showed that only simultaneous targeting of Her2 and cMet was successful in sensitizing TNBC to RT and preventing its regrowth. The strategy presented herein holds the potential to be broadly applicable in clinical use. HighlightsO_LISensitization of TNBC to radiotherapy (RT) is a clinically unmet need C_LIO_LISingle cell strategy creates a precise map of subpopulations expanding post-RT C_LIO_LIEvolution of intra-tumor heterogeneity is turned into a therapeutic advantage C_LIO_LISimultaneous targeting of expanding subpopulations sensitizes TNBC to radiotherapy C_LI

cancer biology↗