Journal Article

Transcriptional Profiling of Ectoderm Specification to Keratinocyte Fate in Human Embryonic Stem Cells

Hou, Lin, Tadeu, Ana Mafalda Baptista, Zhao, Hongyu, Horsley, Valerie, Lin, Samantha, Chung, Lisa, Zhong, Mei

2015

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Binding sites / Cell adhesion & migration / Cell cycle / Cell differentiation / Cell Differentiation - drug effects / Cells, Cultured / Deoxyribonucleic acid / Dermatology / Developmental biology / Differentiation (biology) / Dipeptides - pharmacology / DNA / DNA polymerase / Down-Regulation - drug effects / Ectoderm / Ectoderm - cytology / Ectoderm - metabolism / Embryo cells / Embryo, Mammalian - metabolism / Embryogenesis / Embryonic stem cells / Gene expression / Gene Expression Profiling / Gene regulation / Gene sequencing / Genes / Genetic aspects / Growth factors / Homeostasis / Human Embryonic Stem Cells - cytology / Human Embryonic Stem Cells - drug effects / Human Embryonic Stem Cells - metabolism / Humans / Keratinocytes - cytology / Keratinocytes - metabolism / Ligands / Mice / Phosphorylation / Profiling / Proteins / Public health / Ribonucleic acid / RNA / RNA sequencing / Secretase / Sequence Analysis, RNA / Skin / Skin diseases / Specifications / Stem cells / Transcription / Transcription (Genetics) / Up-Regulation - drug effects