M3i

@article{muller_development_2018,

title = {Development of an innervated tissue-engineered skin with human sensory neurons and Schwann cells differentiated from iPS cells},

author = {Quentin Muller and Marie-Josée Beaudet and Thiéry De Serres-Bérard and Sabrina Bellenfant and Vincent Flacher and François Berthod},

doi = {10.1016/j.actbio.2018.10.011},

issn = {1878-7568},

year  = {2018},

date = {2018-01-01},

journal = {Acta Biomaterialia},

volume = {82},

pages = {93--101},

abstract = {Cutaneous innervation is increasingly recognized as a major element of skin physiopathology through the neurogenic inflammation driven by neuropeptides that are sensed by endothelial cells and the immune system. To investigate this process in vitro, models of innervated tissue-engineered skin (TES) were developed, yet exclusively with murine sensory neurons extracted from dorsal root ganglions. In order to build a fully human model of innervated TES, we used induced pluripotent stem cells (iPSC) generated from human skin fibroblasts. Nearly 100% of the iPSC differentiated into sensory neurons were shown to express the neuronal markers BRN3A and β3-tubulin after 19 days of maturation. In addition, these cells were also positive to TRPV1 and neurofilament M, and some of them expressed Substance P, TrkA and TRPA1. When stimulated with molecules inducing neuropeptide release, iPSC-derived neurons released Substance P and CGRP, both in conventional monolayer culture and after seeding in a 3D fibroblast-populated collagen sponge model. Schwann cells, the essential partners of neurons for function and axonal migration, were also successfully differentiated from human iPSC as shown by their expression of the markers S100, GFAP, p75 and SOX10. When cultured for one additional month in the TES model, iPSC-derived neurons seeded at the bottom of the sponge formed a network of neurites spanning the whole TES up to the epidermis, but only when combined with mouse or iPSC-derived Schwann cells. This unique model of human innervated TES should be highly useful for the study of cutaneous neuroinflammation. STATEMENT OF SIGNIFICANCE: The purpose of this work was to develop in vitro an innovative fully human tissue-engineered skin enabling the investigation of the influence of cutaneous innervation on skin pathophysiology. To reach that aim, neurons were differentiated from human induced pluripotent stem cells (iPSCs) generated from normal human skin fibroblasts. This innervated tissue-engineered skin model will be the first one to show iPSC-derived neurons can be successfully used to build a 3D nerve network in vitro. Since innervation has been recently recognized to play a central role in many human skin diseases, such as psoriasis and atopic dermatitis, this construct promises to be at the forefront to model these diseases while using patient-derived cells.},

keywords = {atopic dermatitis, Axonal migration, Biological, Canada, Cells, CGRP, Chemistry, COLLAGEN, Culture, Dermatitis, development, disease, Endothelial Cells, ENDOTHELIAL-CELLS, Epidermis, Expression, Fibroblast, Fibroblasts, function, Human, Humans, Immune System, Immunology, immunopathology, IN VITRO, Induced Pluripotent Stem Cells, inflammation, INNERVATION, Maturation, migration, Models, mouse, murine, Nerve, Neurites, Neurogenic Inflammation, Neurons, NEUROPEPTIDE, Neuropeptides, physiopathology, Pluripotent Stem Cells, Psoriasis, SCHWANN CELLS, Sensory Receptor Cells, Skin, skin disease, Skin Diseases, stem, Stem Cells, SUBSTANCE, SUBSTANCE P, Team-Mueller, Tissue Engineering, TRPV1},

pubstate = {published},

tppubtype = {article}

}

@article{amcheslavsky_enteroendocrine_2014b,

title = {Enteroendocrine cells support intestinal stem-cell-mediated homeostasis in Drosophila},

author = {Alla Amcheslavsky and Wei Song and Qi Li and Yingchao Nie and Ivan Bragatto and Dominique Ferrandon and Norbert Perrimon and Tony Y Ip},

doi = {10.1016/j.celrep.2014.08.052},

issn = {2211-1247},

year  = {2014},

date = {2014-10-01},

journal = {Cell Rep},

volume = {9},

number = {1},

pages = {32--39},

abstract = {Intestinal stem cells in the adult Drosophila midgut are regulated by growth factors produced from the surrounding niche cells including enterocytes and visceral muscle. The role of the other major cell type, the secretory enteroendocrine cells, in regulating intestinal stem cells remains unclear. We show here that newly eclosed scute loss-of-function mutant flies are completely devoid of enteroendocrine cells. These enteroendocrine cell-less flies have normal ingestion and fecundity but shorter lifespan. Moreover, in these newly eclosed mutant flies, the diet-stimulated midgut growth that depends on the insulin-like peptide 3 expression in the surrounding muscle is defective. The depletion of Tachykinin-producing enteroendocrine cells or knockdown of Tachykinin leads to a similar although less severe phenotype. These results establish that enteroendocrine cells serve as an important link between diet and visceral muscle expression of an insulin-like growth factor to stimulate intestinal stem cell proliferation and tissue growth.},

keywords = {Animals, Cell Differentiation, Enterocytes, Enteroendocrine Cells, Female, ferrandon, Homeostasis, Intestines, M3i, Male, Stem Cells, Tachykinins},

pubstate = {published},

tppubtype = {article}

}

@article{duheron_receptor_2011,

title = {Receptor activator of NF-kappaB (RANK) stimulates the proliferation of epithelial cells of the epidermo-pilosebaceous unit},

author = {V Duheron and E Hess and M Duval and M Decossas and B Castaneda and J E Klopper and L Amoasii and J B Barbaroux and I R Williams and H Yagita and J Penninger and Y Choi and F Lezot and R Groves and R Paus and C G Mueller},

doi = {10.1073/pnas.1013054108},

year  = {2011},

date = {2011-03-01},

journal = {Proc.Natl.Acad.Sci.U.S.A},

volume = {108},

number = {1091-6490 (Electronic)},

pages = {5342--5347},

abstract = {Receptor activator of NF-kappaB (RANK), known for controlling bone mass, has been recognized for its role in epithelial cell activation of the mammary gland. Because bone and the epidermo-pilosebaceous unit of the skin share a lifelong renewal activity where similar molecular players operate, and because mammary glands and hair follicles are both skin appendages, we have addressed the function of RANK in the hair follicle and the epidermis. Here, we show that mice deficient in RANK ligand (RANKL) are unable to initiate a new growth phase of the hair cycle and display arrested epidermal homeostasis. However, transgenic mice overexpressing RANK in the hair follicle or administration of recombinant RANKL both activate the hair cycle and epidermal growth. RANK is expressed by the hair follicle germ and bulge stem cells and the epidermal basal cells, cell types implicated in the renewal of the epidermo-pilosebaceous unit. RANK signaling is dispensable for the formation of the stem cell compartment and the inductive hair follicle mesenchyme, and the hair cycle can be rescued by Rankl knockout skin transplantation onto nude mice. RANKL is actively transcribed by the hair follicle at initiation of its growth phase, providing a mechanism for stem cell RANK engagement and hair-cycle entry. Thus, RANK-RANKL regulates hair renewal and epidermal homeostasis and provides a link between these two activities},

keywords = {Activation, Animals, Cell Proliferation, Chemistry, cytology, Epidermis, Epithelial Cells, function, Genetics, Growth, Hair, hair follicle, Homeostasis, Immunology, Inbred C57BL, ligand, metabolism, Mice, NF-kappa B, NF-kappaB, Nude, Osteoprotegerin, physiology, Proliferation, rank, RANK ligand, Receptor, Receptor Activator of Nuclear Factor-kappa B, signaling, Skin, Skin Transplantation, stem, Stem Cells, Team-Mueller, transgenic, TRANSGENIC MICE, TRANSPLANTATION},

pubstate = {published},

tppubtype = {article}

}

@article{cronin_genome-wide_2009b,

title = {Genome-wide RNAi screen identifies genes involved in intestinal pathogenic bacterial infection},

author = {Shane J F Cronin and Nadine T Nehme and Stefanie Limmer and Samuel Liegeois and Andrew J Pospisilik and Daniel Schramek and Andreas Leibbrandt and Ricardo Matos de Simoes and Susanne Gruber and Urszula Puc and Ingo Ebersberger and Tamara Zoranovic and Gregory G Neely and Arndt von Haeseler and Dominique Ferrandon and Josef M Penninger},

doi = {10.1126/science.1173164},

issn = {1095-9203},

year  = {2009},

date = {2009-01-01},

journal = {Science},

volume = {325},

number = {5938},

pages = {340--343},

abstract = {Innate immunity represents the first line of defense in animals. We report a genome-wide in vivo Drosophila RNA interference screen to uncover genes involved in susceptibility or resistance to intestinal infection with the bacterium Serratia marcescens. We first employed whole-organism gene suppression, followed by tissue-specific silencing in gut epithelium or hemocytes to identify several hundred genes involved in intestinal antibacterial immunity. Among the pathways identified, we showed that the JAK-STAT signaling pathway controls host defense in the gut by regulating stem cell proliferation and thus epithelial cell homeostasis. Therefore, we revealed multiple genes involved in antibacterial defense and the regulation of innate immunity.},

keywords = {*Genome, *RNA Interference, Animal, Animals, Cell Proliferation, Drosophila melanogaster/*genetics/immunology/*microbiology, Drosophila Proteins/genetics/metabolism, Epithelial Cells, Epithelial Cells/cytology/physiology, ferrandon, Genetically Modified, Genome, Hemocytes, Hemocytes/immunology/metabolism/microbiology, Homeostasis, Immunity, Innate, Innate/*genetics, Insect, Intestinal Mucosa, Intestinal Mucosa/cytology/immunology/metabolism/microbiology, Janus Kinases, Janus Kinases/genetics/metabolism, M3i, Models, RNA Interference, Serratia Infections, Serratia Infections/genetics/*immunology/microbiology, Serratia marcescens, Serratia marcescens/*immunology/physiology, Signal Transduction, STAT Transcription Factors, STAT Transcription Factors/genetics/metabolism, Stem Cells, Stem Cells/cytology/physiology},

pubstate = {published},

tppubtype = {article}

}