Embryonic stem cells as an ectodermal cellular model of human p63-related dysplasia syndromes
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- 作者：Philippe Rostagno ; Zohar Wolchinsky ; Aless ; ra M. Vigano ; Shoham Shivtiel ; Huiqing Zhou ; Hans Van Bokhoven ; Giustina Ferone ; Caterina Missero ; Roberto Mantovani ; Daniel Aberdam ; Thierry Virolle
- 关键词：p63 ; Embryonic stem cells ; Ectodermal dysplasia ; Epidermal fate
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2010
- 出版时间：23 April 2010
- 年：2010
- 卷：395
- 期：1
- 页码：131-135
- 全文大小：461 K
文摘
Heterozygous mutations in the TP63 transcription factor underlie the molecular basis of several similar autosomal dominant ectodermal dysplasia (ED) syndromes. Here we provide a novel cellular model derived from embryonic stem (ES) cells that recapitulates in vitro the main steps of embryonic skin development. We show that ES cells carrying AEC or EEC mutations are unable to differentiate into the epidermal fate. Comparative transcriptome analysis strongly reveals an embryonic epidermal signature and suggests that mutations in the SAM domain (AEC) provide activating properties while mutations in the DBD domain (EEC) induce strong inhibitory capabilities. Our model uncovers the effect of relevant ED mutations that otherwise are difficult to evaluate on the ectodermal embryonic stage, an embryonic event critical for proper skin formation.