Embryonic stem cells as an ectodermal cellular model of human p63-related dysplasia syndromes.
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.
Rostagno
Philippe
P
INSERM U898, Nice, France.
Wolchinsky
Zohar
Z
Vigano
Alessandra M
AM
Shivtiel
Shoham
S
Zhou
Huiqing
H
Van Bokhoven
Hans
H
Ferone
Giustina
G
Missero
Caterina
C
Mantovani
Roberto
R
Aberdam
Daniel
D
Virolle
Thierry
T
D000818:Animals; D002478:Cells, Cultured; D004476:Ectodermal Dysplasia / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D012867:Skin / Q000196:embryology*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins