title: 3D In vitro model of a functional epidermal permeability barrier from human embryonic stem cells and induced pluripotent stem cells.
abstract: Cornification and epidermal barrier defects are associated with a number of clinically diverse skin disorders. However, a suitable in vitro model for studying normal barrier function and barrier defects is still lacking. Here, we demonstrate the generation of human epidermal equivalents (HEEs) from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). HEEs are structurally similar to native epidermis, with a functional permeability barrier. We exposed a pure population of hESC/iPSC-derived keratinocytes, whose transcriptome corresponds to the gene signature of normal primary human keratinocytes (NHKs), to a sequential high-to-low humidity environment in an air/liquid interface culture. The resulting HEEs had all of the cellular strata of the human epidermis, with skin barrier properties similar to those of normal skin. Such HEEs generated from disease-specific iPSCs will be an invaluable tool not only for dissecting molecular mechanisms that lead to epidermal barrier defects but also for drug development and screening.
authors.affiliation: Stem Cell Laboratory, Assisted Conception Unit, Division of Women's Health, Women's Health Academic Centre, King's College London, London SE1 9RT, UK ; St John's Institute of Dermatology, King's College London, London SE1 9RT, UK.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Petrova
authors.affiliation: Department of Dermatology, Veteran Affairs Medical Center, University of California, San Francisco, San Francisco, CA 94121, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Celli
authors.affiliation: Stem Cell Laboratory, Assisted Conception Unit, Division of Women's Health, Women's Health Academic Centre, King's College London, London SE1 9RT, UK.
authors.forename: Laureen
authors.initials: L
authors.lastname: Jacquet
authors.affiliation: Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London SE1 9RT, UK.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Dafou
authors.affiliation: Department of Dermatology, Veteran Affairs Medical Center, University of California, San Francisco, San Francisco, CA 94121, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Crumrine
authors.affiliation: Department of Dermatology, Veteran Affairs Medical Center, University of California, San Francisco, San Francisco, CA 94121, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Hupe
authors.affiliation: Genomics Centre, King's College London, London SE1 9NH, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Arno
authors.affiliation: Histology Laboratory, Wolfson Centre for Age-Related Diseases, School of Biomedical Sciences, King's College London, London SE1 1UL, UK.
authors.forename: Carl
authors.initials: C
authors.lastname: Hobbs
authors.affiliation: Genomic Medicine, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Cvoro
authors.affiliation: St John's Institute of Dermatology, King's College London, London SE1 9RT, UK.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Karagiannis
authors.affiliation: Stem Cell Laboratory, Assisted Conception Unit, Division of Women's Health, Women's Health Academic Centre, King's College London, London SE1 9RT, UK.
authors.forename: Liani
authors.initials: L
authors.lastname: Devito
authors.affiliation: Department of Dermatology, Veteran Affairs Medical Center, University of California, San Francisco, San Francisco, CA 94121, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Dermatology, Veteran Affairs Medical Center, University of California, San Francisco, San Francisco, CA 94121, USA.
authors.forename: Lillian C
authors.initials: LC
authors.lastname: Adame
authors.affiliation: Clinical Transplantation Laboratory, GSTS and MRC Centre for Transplantation, King's College London, King's Health Partners, London SE1 9RT, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Vaughan
authors.affiliation: St John's Institute of Dermatology, King's College London, London SE1 9RT, UK.
authors.forename: John A
authors.initials: JA
authors.lastname: McGrath
authors.affiliation: Department of Dermatology, Veteran Affairs Medical Center, University of California, San Francisco, San Francisco, CA 94121, USA.
authors.forename: Theodora M
authors.initials: TM
authors.lastname: Mauro
authors.affiliation: Stem Cell Laboratory, Assisted Conception Unit, Division of Women's Health, Women's Health Academic Centre, King's College London, London SE1 9RT, UK.
authors.forename: Dusko
authors.initials: D
authors.lastname: Ilic
mesh_terms: D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D053547:Keratin-14 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008954:Models, Biological; D010539:Permeability; D025341:Principal Component Analysis; D013724:Teratoma / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: C507540:KRT14 protein, human; D053547:Keratin-14; D014157:Transcription Factors