Embryonic stem cells as an ectodermal cellular model of human p63-related dysplasia syndromes

作者：Rostagno Philippe; Wolchinsky Zohar; Vigano Alessandra M; Shivtiel Shoham; Zhou Huiqing; Van Bokhoven Hans; Ferone Giustina; Missero Caterina; Mantovani Roberto; Aberdam Daniel^*; Virolle Thierry

来源：Biochemical and Biophysical Research Communications, 2010, 395(1): 131-135.

DOI：10.1016/j.bbrc.2010.03.154

• p63
• Embryonic stem cells
• Ectodermal dysplasia
• Epidermal fate

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.

• 出版日期2010-4-23