title: Transcriptional profiling of ectoderm specification to keratinocyte fate in human embryonic stem cells.
abstract: In recent years, several studies have shed light into the processes that regulate epidermal specification and homeostasis. We previously showed that a broad-spectrum γ-secretase inhibitor DAPT promoted early keratinocyte specification in human embryonic stem cells triggered to undergo ectoderm specification. Here, we show that DAPT accelerates human embryonic stem cell differentiation and induces expression of the ectoderm protein AP2. Furthermore, we utilize RNA sequencing to identify several candidate regulators of ectoderm specification including those involved in epithelial and epidermal development in human embryonic stem cells. Genes associated with transcriptional regulation and growth factor activity are significantly enriched upon DAPT treatment during specification of human embryonic stem cells to the ectoderm lineage. The human ectoderm cell signature identified in this study contains several genes expressed in ectodermal and epithelial tissues. Importantly, these genes are also associated with skin disorders and ectodermal defects, providing a platform for understanding the biology of human epidermal keratinocyte development under diseased and homeostatic conditions.
authors: Yale University, Department of Molecular, Cell and Developmental Biology, New Haven, CT, 06511, United States of America.
authors: Ana Mafalda Baptista
authors: AM
authors: Tadeu
authors: Yale University, Department of Molecular, Cell and Developmental Biology, New Haven, CT, 06511, United States of America.
authors: Samantha
authors: S
authors: Lin
authors: Yale University, Department of Biostatistics, Yale School of Public Health, New Haven, CT, 06520, United States of America.
authors: Lin
authors: L
authors: Hou
authors: Yale University, Department of Biostatistics, Yale School of Public Health, New Haven, CT, 06520, United States of America.
authors: Lisa
authors: L
authors: Chung
authors: Yale University, Yale Stem Cell Center, Genomics Facility, New Haven, CT, 06520, United States of America.
authors: Mei
authors: M
authors: Zhong
authors: Yale University, Department of Biostatistics, Yale School of Public Health, New Haven, CT, 06520, United States of America.
authors: Hongyu
authors: H
authors: Zhao
authors: Yale University, Department of Molecular, Cell and Developmental Biology, New Haven, CT, 06511, United States of America.
authors: Valerie
authors: V
authors: Horsley
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004151:Dipeptides / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004475:Ectoderm / Q000166:cytology / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D020869:Gene Expression Profiling; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D017423:Sequence Analysis, RNA; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004151:Dipeptides; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester