Tadeu Ana Mafalda Baptista, Lin Samantha, Hou Lin, Chung Lisa, Zhong Mei, Zhao Hongyu, Horsley Valerie
Yale University, Department of Molecular, Cell and Developmental Biology, New Haven, CT, 06511, United States of America.
Yale University, Department of Biostatistics, Yale School of Public Health, New Haven, CT, 06520, United States of America.
PLoS One. 2015 Apr 7;10(4):e0122493. doi: 10.1371/journal.pone.0122493. eCollection 2015.
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.
近年来，多项研究揭示了调节表皮特化和稳态的过程。我们之前表明，一种广谱γ-分泌酶抑制剂DAPT在诱导人胚胎干细胞进行外胚层特化时促进了早期角质形成细胞的特化。在此，我们表明DAPT加速人胚胎干细胞分化并诱导外胚层蛋白AP2的表达。此外，我们利用RNA测序来鉴定外胚层特化的几个候选调节因子，包括那些参与人胚胎干细胞上皮和表皮发育的因子。在人胚胎干细胞向外胚层谱系特化过程中，与转录调控和生长因子活性相关的基因在DAPT处理后显著富集。本研究中鉴定出的人外胚层细胞特征包含在外胚层和上皮组织中表达的几个基因。重要的是，这些基因也与皮肤疾病和外胚层缺陷相关，为理解患病和稳态条件下人表皮角质形成细胞发育的生物学提供了一个平台。
