Merkel Cells as Putative Regulatory Cells in Skin Disorders: An In Vitro Study

Merkel cells (MCs) are involved in mechanoreception, but several lines of evidence suggest that they may also participate in skin disorders through the release of neuropeptides and hormones. In addition, MC hyperplasias have been reported in inflammatory skin diseases. However, neither proliferation nor reactions to the epidermal environment have been demonstrated. We established a culture model enriched in swine MCs to analyze their proliferative capability and to discover MC survival factors and modulators of MC neuroendocrine properties. In culture, MCs reacted to bFGF by extending outgrowths. Conversely, neurotrophins failed to induce cell spreading, suggesting that they do not act as a growth factor for MCs. For the first time, we provide evidence of proliferation in culture through Ki-67 immunoreactivity. We also found that MCs reacted to histamine or activation of the proton gated/osmoreceptor TRPV4 by releasing vasoactive intestinal peptide (VIP). Since VIP is involved in many pathophysiological processes, its release suggests a putative regulatory role for MCs in skin disorders. Moreover, in contrast to mechanotransduction, neuropeptide exocytosis was Ca2+-independent, as inhibition of Ca2+ channels or culture in the absence of Ca2+ failed to decrease the amount of VIP released. We conclude that neuropeptide release and neurotransmitter exocytosis may be two distinct pathways that are differentially regulated

Determination of chemical irritation potential using a defined gene signature set on tissue-engineered human skin equivalents

There are no physical or visual manifestations that define skin sensitivity or irritation; a subjective diagnosis is made based on the evaluation of clinical presentations including burning, prickling, erythema and itching. Adverse skin reaction in response to topically applied products is common and can limit the use of dermatological or cosmetic products. The purpose of this study was to evaluate the use of human skin equivalents (HSE) based on immortalised skin keratinocytes and evaluate the potential of a 22-gene panel in combination with multivariate analysis to discriminate between chemicals known to act as irritants and those that do not. Test compounds were applied topically to full thickness HSE or human ex vivo skin and gene signatures determined for known irritants and non-irritants. Principle component analysis showed the discriminatory potential of the 22-gene panel. Linear discrimination analysis, performed to further refine the gene set for a more high-throughput analysis, identified a putative seven-gene panel (IL-6, PTGS2, ATF3, TRPV3, MAP3K8, HMGB2 and MMP-3) that could distinguish potential irritants from non-irritants. These data offer promise as an in vitro prediction tool, although analysis of a large chemical test set is required to further evaluate the system

Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis

Collagen-producing cells maintain the complex architecture of the lung and drive pathologic scarring in pulmonary fibrosis. Here we perform single-cell RNA-sequencing to identify all collagen-producing cells in normal and fibrotic lungs. We characterize multiple collagen-producing subpopulations with distinct anatomical localizations in different compartments of murine lungs. One subpopulation, characterized by expression of Cthrc1 (collagen triple helix repeat containing 1), emerges in fibrotic lungs and expresses the highest levels of collagens. Single-cell RNA-sequencing of human lungs, including those from idiopathic pulmonary fibrosis and scleroderma patients, demonstrate similar heterogeneity and CTHRC1-expressing fibroblasts present uniquely in fibrotic lungs. Immunostaining and in situ hybridization show that these cells are concentrated within fibroblastic foci. We purify collagen-producing subpopulations and find disease-relevant phenotypes of Cthrc1-expressing fibroblasts in in vitro and adoptive transfer experiments. Our atlas of collagen-producing cells provides a roadmap for studying the roles of these unique populations in homeostasis and pathologic fibrosis

Implantation du quinoa et simulation de sa culture sur l'Altiplano Bolivien

Quinoa is a pseudo cereal of South America, grown mainly in the Andean region on the Bolivian and Peruvian Altiplano. Today, about 25000 tons are produced annually in Bolivia, which became the first exporter in the world. However, the Bolivian Altiplano, which has an average altitude of 3800m, is a harsh environment, where the risks of drought and frost during the crop cycle are very important and provoke low crop yields, highly variable from one year to the other. Because of these limiting climatic conditions, germination and emergence are the main critical phases of the culture of quinoa. The objective of this work was to study those phenomena by modeling, through the adaptation of a generic crop model, STICS, to quinoa and climatic and cropping conditions of the Bolivian Altiplano. Data sets were formed through experiments in three sites from north to south of the Altiplano. At first, crop establishment was studied alone, by a numerical experimentation testing various cultural practices, in order to see the adaptation of the cropping system. The second stage is the model calibration. After analyzing the existing formalisms and determining of the need for new ones or modifications, the parameters were set, based on experimental measurements, bibliography or optimization. The results prove to be quite satisfying. Finally, in the third stage, the impact of implantation techniques on yield was tested. Different rotations were also simulated (fallow-quinoa, fallow-fallow-quinoa, or quinoa-quinoa) to see their influence on the water and nitrogen soil balance, crop establishment and crop yield.Le quinoa est une pseudocéréale d'Amérique du Sud, cultivé essentiellement en région andine sur les Altiplanos boliviens et péruviens. Aujourd'hui, environ 25 000 tonnes sont produites annuellement en Bolivie, qui est devenu le premier exportateur mondial. Toutefois, l'Altiplano bolivien, d'altitude moyenne 3800m, est un milieu difficile, où les risques élevés de sécheresse et de gel pendant le cycle de culture sont à l'origine de rendements agricoles faibles et très variables. Ces conditions climatiques limitantes font de la germination et de la levée la principale phase critique de la culture du quinoa. Ce travail a eu comme objectif l'analyse de ces questions par modélisation, par le biais de l'adaptation d'un modèle générique de fonctionnement des cultures, STICS, au quinoa dans les conditions climatiques et culturales de l'Altiplano bolivien. Pour cela, des jeux de données ont été constitués grâce à des expérimentations en trois sites répartis du Nord au Sud de l'Altiplano. Dans un premier temps, l'implantation de la culture a été étudiée seule, par expérimentation numérique en testant différents itinéraires techniques. Le deuxième temps a consisté en la calibration du modèle pour le quinoa. Après analyse des formalismes existants et détermination du besoin d'ajouts ou de modifications de formalismes, les paramètres ont été déterminés. Les résultats obtenus s'avèrent assez satisfaisants. Enfin, dans un troisième temps, l'impact des techniques d'implantation sur le rendement a été testé. Différentes successions culturales ont également été simulées, afin de voir leur influence sur l'état hydrique et azoté du sol et sur l'implantation et le rendement de la culture

Automatisation de la quantification des images biomedicales: applications au marquage cytochimique et a la reconstruction stereographique

SIGLEINIST T 76536 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Intraepidermal nerve fibres are not the exclusive tranducers of nociception

International audienc

Passage de STICS4 à STICS5: mise à jour du paramétrage plante et illustration à partir d'une base de données cultures

National audienc