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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Ectoderm specification of H1 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. 6 samples were analyzed, 3 replicates of ETOH treated H1 HESCs and 3 replicates of DAPT treated H1 HESCs

ORGANISM(S): Homo sapiens

SUBMITTER: Valerie horsley

PROVIDER: E-GEOD-66506 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Ectoderm specification of H1 human embryonic stem cells

Project description: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.

2015-03-05 | GSE66506 | GEO

Stagewise keratinocyte differentiation from human embryonic stem cells by defined signal transduction modulators

Project description:we use human embryonic stem cells to demonstrate that epidermal ectoderm and subsequent keratinocyte cell fate can be determined step by step under the regulation of defined factors. We show the global gene expression profiles clustered according to the differentiation stages . We also found the human keratinocyte specific gene expression according to the differentiation stages.

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Homo sapiens

Project description:Ectoderm specification of H1 human embryonic stem cells

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Fate specification of neural plate border by canonical Wnt signaling and Grhl3 is crucial for neural tube closure.

Project description:During primary neurulation, the separation of a single-layered ectodermal sheet into the surface ectoderm (SE) and neural tube specifies SE and neural ectoderm (NE) cell fates. The mechanisms underlying fate specification in conjunction with neural tube closure are poorly understood. Here, by comparing expression profiles between SE and NE lineages, we observed that uncommitted progenitor cells, expressing stem cell markers, are present in the neural plate border/neural fold prior to neural tube closure. To identify what type of signaling pathways and transcriptional factors are involved in the fate specification between SE and NE cells during neurulation.

2015-04-17 | E-GEOD-67977 | biostudies-arrayexpress

E2A regulates neural ectoderm fate specification in human embryonic stem cells

Project description:E2A regulates neural ectoderm fate specification in human embryonic stem cells

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Fate specification of neural plate border by canonical Wnt signaling and Grhl3 is crucial for neural tube closure.

2015-04-17 | GSE67977 | GEO

Mutant p63 affects epidermal cell identity through rewiring the enhancer landscape

Project description:<p>Transcription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. Mutations in the p63 DNA-binding domain are associated with Ectrodactyly Ectodermal Dysplasia Cleft Lip/Palate (EEC) syndrome. Underlying molecular mechanism of these mutations however remain unclear. Here we characterized the transcriptome and epigenome of p63 mutant keratinocytes derived from EEC patients. The transcriptome of p63 mutant keratinocytes deviated from the normal epidermal cell identity. Epigenomic analyses showed an altered enhancer landscape in p63 mutant keratinocytes contributed by loss of p63-bound active enhancers and by unexpected gain of enhancers. The gained enhancers were frequently bound by deregulated transcription factors such as RUNX1. Reversing RUNX1 overexpression partially rescued deregulated gene expression and the altered enhancer landscape. Our findings identify an unreported disease mechanism whereby mutant p63 rewires the enhancer landscape and affects epidermal cell identity, consolidating the pivotal role of p63 in controlling the enhancer landscape of epidermal keratinocytes.</p>

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A Molecular Atlas of the Developing Ectoderm Defines Neural, Neural Crest, Placode and Non-Neural Progenitor Identity in Vertebrates.

Project description:During vertebrate neurulation, the embryonic ectoderm is patterned into lineage progenitors for neural plate, neural crest, placodes and epidermis. Here, we use Xenopus laevis embryos to analyze the spatial and temporal transcriptome of distinct ectodermal domains in the course of neurulation, during the establishment of cell lineages. In order to define the transcriptome of small groups of cells from a single germ layer, and to retain spatial information, dorsal and ventral ectoderm was subdivided along the anterior-posterior and medial-lateral axes by microdissections. Principal Component Analysis on the transcriptomes of these ectoderm fragments primarily identifies embryonic axes and temporal dynamics. This provides a genetic code to define positional information of any ectoderm sample along the anterior-posterior and dorsal-ventral axes, directly from its transcriptome. In parallel, we use Non-Negative Matrix Factorization to predict enhanced gene expression maps onto early and mid-neurula embryos, and specific signatures for each ectoderm area. The clustering of spatial and temporal datasets allowed detection of multiple biologically relevant groups (e.g. Wnt signaling, neural crest development, sensory placode specification, ciliogenesis, germ layer specification). We provide an interactive network interface, EctoMap, for exploring synexpression relationships among genes expressed in the neurula, and suggest several strategies to use this comprehensive dataset to address questions in developmental biology as well as stem cell or cancer research.

2017-10-25 | GSE103240 | GEO

Generation of induced keratinocyte stem cells from human urine cells by defined transcription factors

Project description:Analysis of induced keratinocyte stem cells from male/female urine cells (MiKSC/FiKSC) by defined transcription factors vs. foreskin derived primary human neonatal epidermal keratinocytes (pKC) and male/female urine cells (MUC/FUC). Results provide insight into molecular similarities between induced keratinocyte stem cells and human foreskin derived primary human neonatal epidermal keratinocytes.

2019-04-11 | GSE129316 | GEO

Optogenetic manipulation of BMP signalling to drive chondrogenic differentiation of hPSCs

Project description:Optogenetics is a rapidly advancing technology that combines photochemical, optical and synthetic biology techniques to control cellular behaviour and physiology. Combining sensitive light responsive optogenetic intervention tools with human pluripotent stem cell differentiation models has the potential to refine differentiation and unpick the processes by which morphogenetic signals direct tissue patterning, organisation and cell specification. Here, we utilised an optogenetic bone morphogenetic protein (BMP) signalling system (optoBMP) to drive chondrogenic differentiation of human embryonic stem cells (hESCs). We initially engineered light-sensitive hESCs through CRISPR/Cas9-mediated integration of the optoBMP system into the AAVS1 locus. Activation of optoBMP with blue light in lieu of BMP family growth factors during differentiation resulted in activation of BMP signalling pathway mechanisms and upregulation of a chondrogenic phenotype, with significant transcriptional differences compared to cells left in the dark. Furthermore, cells differentiated with light were capable of forming chondrogenic pellets consisting of a hyaline-like cartilaginous matrix.

2023-11-09 | E-MTAB-13377 | biostudies-arrayexpress

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