Biology subjects

Foresti, R.

Publications and source records attributed to Foresti, R..

3 recordsLinked to original sources

bioRxiv2024

Non-canonical nuclear function of glutaminase cooperates with Wnt signaling to drive EMT during neural crest development

Metabolic reprograming has been linked to epithelial-to-mesenchymal transition (EMT) in cancer cells, but how it influences EMT in normal cells remains largely unknown. Here we explored how metabolism impacts delamination and migration of avian trunk neural crest cells, an important stem cell population of the vertebrate embryo. We report that delamination exhibits a quiescent metabolic phenotype whereas migration is characterized by OXPHOS-driven metabolism coupled to distinct expression of metabolic, EMT and developmental genes. While glucose and glutamine are required for delamination and migration, we uncover a novel role for glutamine and its catabolizing enzyme glutaminase in delamination. Specifically, glutamine is required for nuclear translocation of glutaminase, which interacts and cooperates with Wnt signaling to regulate EMT gene expression and cell cycle during delamination. Our data indicate that similarly to cancer cells, embryonic cells engage metabolic enzymes for non-canonical signaling functions to connect metabolism with EMT.

developmental biology↗

bioRxiv2022

Glucose oxidation and nutrients availability drive neural crest development

Bioenergetic metabolism is a key regulator of cellular function and signaling activity but the exact roles of nutrient utilization and energy production in embryonic development remain unknown. Here we investigated the metabolic pathways and deciphered the role of carbon metabolism required for the development of neural crest cells (NCC), a migratory stem cell population of the vertebrate embryo. We uncovered that glucose oxidation constitutes the prominent metabolic signature of trunk NCC and supports their delamination, migration, and proliferation. Additionally, we found that glycolysis, mitochondrial respiration and the pentose phosphate pathway are all mobilized downstream of glucose uptake. These metabolic pathways do not support specific cellular processes but cooperate and are integrated to accomplish epithelium-to-mesenchyme transition, adhesion, locomotion and proliferation. Moreover, using different nutrient supplies (glucose vs. pyruvate) we show that glucose is crucial to modulate NCC migration and adaptation to environmental stiffness, control NCC stemness and drive their fate decisions through regulation of specific gene expression. Our data establish that NCC development is instructed by metabolic cues that mobilize defined metabolic pathways cooperating together in response to nutrient availability. SUMMARY STATEMENTHere we show that neural crest cell migration and fate decisions rely primarily on glucose oxidation for energy production and mobilize multiple cooperating metabolic pathways for their biosynthetic needs and execution of gene programs.

developmental biology↗

bioRxiv2020

Highly sensitive quantification of carbon monoxide (CO) in vivo reveals a protective role of circulating hemoglobin in CO intoxication

Carbon monoxide (CO) is a gaseous molecule known as the silent killer. It is widely believed that an increase in blood carboxyhemoglobin (CO-Hb) is the best biomarker to define CO intoxication, neglecting the important fact that CO accumulation in tissues is the most likely direct cause of mortality. There is no reliable method other than gas chromatography to accurately determine CO content in tissues. Here we report the properties and usage of hemoCD1, a synthetic supramolecular compound composed of an iron(II)porphyrin and a cyclodextrin dimer, as an accessible reagent for a simple colorimetric assay to quantify CO in biological samples. The assay was validated in various organ tissues collected from rats under normal conditions and after exposure to CO by inhalation. The kinetic profile of CO in blood and tissues after CO treatment suggested that CO accumulation in tissues is prevented by circulating Hb, revealing a protective role of Hb in CO intoxication. Furthermore, hemoCD1 was used in vivo as a CO removal agent, showing that it acts as effective adjuvant to O2 ventilation to eliminate residual CO accumulated in organs, including the brain. These findings open new therapeutic perspectives to counteract the toxicity associated with CO poisoning.

physiology↗