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The remodeling of the human endometrium during the menstrual cycle is based on a tightly regulated spatiotemporal coupling between tissue degradation and regeneration. The respective contributions of the two layers of the endometrium (functionalis and basalis layer) in the regulation of tissue remodeling have been recently questioned, by several laboratories including ours. To clarify the regulatory mechanisms, the identification of molecules subject to a different expression between the two tissue layers is required. Our laboratory collected preliminary results suggesting that the cluster of differentiation CD34, known as a marker of hematopoietic stem cells and endothelial cells, was also expressed by endometrial stromal cells selectively in the funcionalis layer. The first objective of my thesis was to determine the expression profile of CD34 in the human endometrium and identify the variations of his abundance and/or location during the menstrual cycle. To this aim, several endometrial samples were taken from hysterectomy specimens collected at different phases of the menstrual cycle. The CD34 protein was localized in tissue sections by immunohistochemistry and the cells producing CD34 were identified by double immunofluorescence with other cell type's markers. The amounts of CD34 mRNA were measured by RT- qPCR during the menstrual cycle. The results generated hypotheses about the regulation of the expression of CD34 in the endometrium. The second part of my thesis attempted to elucidate these regulatory mechanisms, using different culture models. The nature of the regulators of CD34 expression was investigated by measuring the effects of the addition of estradiol, progesterone, serum or soluble factors in cell or expiant culture. The expression of CD34 was also investigated in a mouse model of human xenograft endometrium, developed in the laboratory. Altogether, my results demonstrate that CD34 is expressed by endometrial fibroblasts specifically in the functional layer, in human and mouse. They highlight a complex regulation most likely involving ovarian steroids and other local signals, in particular from epithelial origin. Finally, they further underline the unique features of endometrial fibroblasts and shed new light on their potential hematopoietic origin and the persistence of (foci from) the functional layer along consecutive menstrual cycles. Le remodelage de l'endomètre humain au cours du cycle menstruel repose sur un couplage spatio-temporel finement régulé entre dégradation et régénération tissulaire . La contribution respective des deux couches de l'endomètre (la couche fonctionnnelle et la couche basale) dans la régulation du remodelage tissulaire est remise en question depuis quelques années, notamment par le laboratoire d'accueil. La clarification des mécani smes régulateurs nécessite l'identification de molécules faisant l'objet d'une expression différente entre les deux couches tissulaires. Le laboratoire d'accueil disposait de résultats préliminaires suggérant que le cluster de différenciation CD34, marqueur connu de cellules souches hématopoïétique s et de cellules endothéliales, était également exprimé par des cellules du stroma endométrial, sélectivement dans la couche superficielle.Le premier objectif de mon mémoire a été de déterminer le profil d'expression de CD34 dans l'endomètre humain et d'identifier les variations de son abondance et/ou de sa localisation au cours du cycle menstruel. Pour cela, des échantillons d'endomètres ont été prélevés sur des pièces d'hystérectomie récoltées aux différentes phases du cycle menstruel. La protéine CD34 a été localisée dans des coupes tissulaires par immunohistochimie et les cellules l'exprimant ont été identifiées par double immunofluore scence avec d'autres marqueurs de types cellulaires. Les quantités d'ARNm de CD34 ont été mesurées par RT­ qPCR au cours du cycle menstruel.Les résultats obtenus ont conduit à formuler des hypothèses concernant la régulation de l'expression de CD34 dans l'endomètre. La seconde partie de mon mémoire a consisté à tenter d'élucider ces mécanismes de régulation grâce à différents modèles de culture. La nature des régulateurs de l'expression de CD34 a été investiguée en mesurant les effets de l'ajout d'œstradiol, de progestérone , de sérum ou de facteurs solubles en culture cellulaire ou d'explants. Les variations d'expression de CD34 ont également été investiguées dans un modèle murin de xénogreffe d'endomètre humain développé au laboratoire. Collectivement, mes observations démontrent l'expression de CD34 par des fibroblastes endométriaux spécifiquement dans la couche fonctionnelle, chez la femme et la souris. Elles mettent en évidence une régulation complexe qui implique probablement les stéroïdes ovariens mais aussi des signaux locaux, notament d'origine épithéliale. Enfin, elles contribuent à souligner les caractéristiques tout à fait particulières des fibroblastes dans l'endomètre et enrichissent le débat sur leur potientielle origine hétopoïétique et sur la persistance de (foyers de) la couche fonctionnelle à travers les cycles menstruels consécutifs.

Endometrium --- Antigens, CD34 --- Menstrual Cycle

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Tissue mechanics and tissue engineering are multidisciplinary and interconnected fields that are studied at multiple scales by integrating knowledge in biology, solid mechanics, fluid dynamics, finite element modeling, imaging, electronics, automation, and design. Experimental, computational, and combined approaches are often used to investigate the structure–function relationships in tissues and to understand how their mechanics and biological pathways are altered in injury, disease, or regeneration. The objective of this Special Issue is to present recent methods for the investigation of tissue mechanics and tissue engineering or for combined research between the two fields.

Technology: general issues --- Chemical engineering --- abdominal aortic aneurysm --- biaxial testing --- mechanical properties --- in vivo strain --- wall shear stress --- inflammation --- regional variations --- heterogeneity --- Goldmann tonometry --- intraocular pressure --- glaucoma --- inflation tests --- pig eyes --- corneal stiffness --- retina --- tissue engineering --- retina regeneration --- biofabrication --- 3D bioprinting --- electrospinning --- ophthalmology --- hematopoietic --- CD34 --- progenitor --- stem cells --- microencapsulation --- chitosan --- alginate --- proliferation --- megakaryocyte --- animal model --- dermal regeneration --- Integra --- Matriderm --- skin substitute --- wound healing --- n/a

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Nephropathic cystinosis (MIM # 219800) is a rare autosomal recessive disorder caused by mutations in the lysosomal cystine transporter cystinosin, encoded by the CTNS gene (17p13.2). This devastating condition initially affects kidneys and subsequently many other organs including eyes, thyroid, pancreas, muscles, and brain. While lysosomal cystine storage is a key feature of the disease and the main target of current therapy, recent groundbreaking research has revealed that cystinosin has diverse functions in cells, being involved in vesicle trafficking, energy homeostasis, and cell death mechanisms. These discoveries deepen our insights into the mechanisms of cystinosis and of lysosomal biology in general. In this Special Issue dedicated to the pioneer of cystinosis research Dr. Jerry Schneider, we highlight the state-of-the-art understanding of cellular and molecular mechanisms of various disease features, opening new horizons for innovative treatment strategies for cystinosis and potentially other lysosomal storage diseases.

Medicine --- Pharmacology --- cystinosis --- cysteamine --- bone --- osteoclast --- genotype --- CD34+ hematopoietic stem and progenitor cells --- gene therapy --- pre-clinical studies --- investigational new drug application --- clinical trial --- disulfiram --- mice --- zebrafish --- fertility --- azoospermia --- hypogonadism --- histopathology --- mouse model --- lysosomal storage disease --- cell and animal models --- infantile nephropathic cystinosis --- bone-muscle wasting --- fibroblast growth factor 23 --- osteoclasts --- sclerostin --- leptin --- fractures --- nephropathic cystinosis --- hollow fiber membrane --- 3-dimensional models --- autophagy --- macrophages --- inflammasome --- proximal tubular cells --- endocytosis --- apoptosis --- chitotriosidase --- interleukins --- galectin-3 --- novel therapies --- endolysosome --- epithelial cell differentiation --- homeostasis --- lysosomal storage diseases --- mitochondrial distress --- kidney proximal tubule --- programmed cell death --- central nervous system --- cortical atrophy --- arterial spin labelling --- cystine blood level --- lysosomal storage disorder --- history --- treatment strategies for cystinosis --- newborn screening --- clinical course --- CTNS-pathogenic variants --- newborn screening for cystinosis --- kidney progenitors --- cell model --- biomarkers --- cystine --- kidney --- therapeutic monitoring --- cystinosis --- cysteamine --- bone --- osteoclast --- genotype --- CD34+ hematopoietic stem and progenitor cells --- gene therapy --- pre-clinical studies --- investigational new drug application --- clinical trial --- disulfiram --- mice --- zebrafish --- fertility --- azoospermia --- hypogonadism --- histopathology --- mouse model --- lysosomal storage disease --- cell and animal models --- infantile nephropathic cystinosis --- bone-muscle wasting --- fibroblast growth factor 23 --- osteoclasts --- sclerostin --- leptin --- fractures --- nephropathic cystinosis --- hollow fiber membrane --- 3-dimensional models --- autophagy --- macrophages --- inflammasome --- proximal tubular cells --- endocytosis --- apoptosis --- chitotriosidase --- interleukins --- galectin-3 --- novel therapies --- endolysosome --- epithelial cell differentiation --- homeostasis --- lysosomal storage diseases --- mitochondrial distress --- kidney proximal tubule --- programmed cell death --- central nervous system --- cortical atrophy --- arterial spin labelling --- cystine blood level --- lysosomal storage disorder --- history --- treatment strategies for cystinosis --- newborn screening --- clinical course --- CTNS-pathogenic variants --- newborn screening for cystinosis --- kidney progenitors --- cell model --- biomarkers --- cystine --- kidney --- therapeutic monitoring