TY - JOUR
T1 - Ablation of coactivator Med1 switches the cell fate of dental epithelia to that generating hair
AU - Yoshizaki, Keigo
AU - Hu, Lizhi
AU - Nguyen, Thai
AU - Sakai, Kiyoshi
AU - He, Bing
AU - Fong, Chak
AU - Yamada, Yoshihiko
AU - Bikle, Daniel D.
AU - Oda, Yuko
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/6/20
Y1 - 2014/6/20
N2 - Cell fates are determined by specific transcriptional programs. Here we provide evidence that the transcriptional coactivator, Mediator 1 (Med1), is essential for the cell fate determination of ectodermal epithelia. Conditional deletion of Med1 in vivo converted dental epithelia into epidermal epithelia, causing defects in enamel organ development while promoting hair formation in the incisors. We identified multiple processes by which hairs are generated in Med1 deficient incisors: 1) dental epithelial stem cells lacking Med 1 fail to commit to the dental lineage, 2) Sox2-expressing stem cells extend into the differentiation zone and remain multi-potent due to reduced Notch1 signaling, and 3) epidermal fate is induced by calcium as demonstrated in dental epithelial cell cultures. These results demonstrate that Med1 is a master regulator in adult stem cells to govern epithelial cell fate.
AB - Cell fates are determined by specific transcriptional programs. Here we provide evidence that the transcriptional coactivator, Mediator 1 (Med1), is essential for the cell fate determination of ectodermal epithelia. Conditional deletion of Med1 in vivo converted dental epithelia into epidermal epithelia, causing defects in enamel organ development while promoting hair formation in the incisors. We identified multiple processes by which hairs are generated in Med1 deficient incisors: 1) dental epithelial stem cells lacking Med 1 fail to commit to the dental lineage, 2) Sox2-expressing stem cells extend into the differentiation zone and remain multi-potent due to reduced Notch1 signaling, and 3) epidermal fate is induced by calcium as demonstrated in dental epithelial cell cultures. These results demonstrate that Med1 is a master regulator in adult stem cells to govern epithelial cell fate.
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U2 - 10.1371/journal.pone.0099991
DO - 10.1371/journal.pone.0099991
M3 - Article
C2 - 24949995
AN - SCOPUS:84903287042
VL - 9
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 6
M1 - e99991
ER -