Biology subjects

Iglesias-Bartolome, R.

Publications and source records attributed to Iglesias-Bartolome, R..

3 recordsLinked to original sources

bioRxiv2023

A GPCR screening in human keratinocytes identifies that the metabolite receptor HCAR3 controls epithelial proliferation, migration, and cellular respiration.

Epithelial cells in the skin and other tissues rely on signals from their environment to maintain homeostasis and respond to injury, and G protein-coupled receptors (GPCRs) play a critical role in this communication. A better understanding of the GPCRs expressed in epithelial cells will contribute to understanding the relationship between cells and their niche and could lead to developing new therapies to modulate cell fate. This study used human primary keratinocytes as a model to investigate the specific GPCRs regulating epithelial cell proliferation and differentiation. We identified three key receptors, hydroxycarboxylic acid-receptor 3 (HCAR3), leukotriene B4-receptor 1 (LTB4R), and G Protein-Coupled Receptor 137 (GPR137) and found that knockdown of these receptors led to changes in numerous gene networks that are important for maintaining cell identity and promoting proliferation while inhibiting differentiation. Our study also revealed that the metabolite receptor HCAR3 regulates keratinocyte migration and cellular metabolism. Knockdown of HCAR3 led to reduced keratinocyte migration and respiration, which could be attributed to altered metabolite use and aberrant mitochondrial morphology caused by the absence of the receptor. This study contributes to understanding the complex interplay between GPCR signaling and epithelial cell fate decisions.

cell biology↗

bioRxiv2021

A biomechanical switch regulates the transition towards homeostasis in esophageal epithelium

Epithelial cells are highly dynamic and can rapidly adapt their behavior in response to tissue perturbations and increasing tissue demands. However, the processes that finely control these responses and, particularly, the mechanisms that ensure the correct switch to and from normal tissue homeostasis are largely unknown. Here we explore changes in cell behavior happening at the interface between postnatal development and homeostasis in the epithelium of the mouse esophagus, as a physiological model exemplifying a rapid but controlled tissue growth transition. Single cell RNA sequencing and histological analysis of the mouse esophagus reveal significant mechanical changes in the epithelium upon tissue maturation. Organ stretching experiments further indicate that tissue strain caused by the differential growth of the mouse esophagus relative to the entire body promotes the emergence of a defined committed population in the progenitor compartment as homeostasis is established. Our results point to a simple mechanism whereby the mechanical changes experienced at the whole tissue level are integrated with those "sensed" at the cellular level to control epithelial cell behavior and tissue maintenance.

cell biology↗

bioRxiv2020

YAP1-TAZ/TEAD transcriptional networks restrain differentiation downstream of oncogenic Hedgehog-SMO activity

Disruption of the transcriptional activity of the Hippo pathway members YAP1 and TAZ has become a major target for cancer treatment. However, detailed analysis of the effectivity and networks affected by YAP1/TAZ transcriptional targeting are limited. Here, by comparing the effects of YAP1/TAZ knockdown with those resulting from TEAD blockage, we unveil the consequences of YAP1/TAZ transcriptional inhibition in cancer cells. We utilize TEADi, an inhibitor of the binding of YAP1 and TAZ with their main transcriptional target TEAD. In a mouse model of basal cell carcinoma (BCC) driven by the smoothened oncogene (SmoM2), TEADi and YAP1/TAZ knockdown lead to reduced proliferation and increased differentiation of tumor cells both in vitro and in vivo. We find that TEAD transcriptional networks inactivate differentiation in BCC by regulating KLF4. Furthermore, we determine YAP1/TAZ TEAD-independent effects in cancer cells that impact Stat3 and NF-{kappa}B gene networks. Our results reveal the TEAD dependent and independent roles of YAP1/TAZ in cancer and expose potential pitfalls for targeting TEAD transcription in tumors.

cancer biology↗