Ablation of coactivator Med1 switches the cell fate of dental epithelia to that generating hair

Keigo Yoshizaki; Lizhi Hu; Thai Nguyen; Kiyoshi Sakai; Bing He; Chak Fong; Yoshihiko Yamada; Daniel D. Bikle; Yuko Oda

doi:10.1371/journal.pone.0099991

Ablation of coactivator Med1 switches the cell fate of dental epithelia to that generating hair

Keigo Yoshizaki, Lizhi Hu, Thai Nguyen, Kiyoshi Sakai, Bing He, Chak Fong, Yoshihiko Yamada, Daniel D. Bikle, Yuko Oda

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

Abstract

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.

Original language	English
Article number	e99991
Journal	PloS one
Volume	9
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0099991
Publication status	Published - Jun 20 2014
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
General

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10.1371/journal.pone.0099991

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abstract = "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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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

PY - 2014/6/20

Y1 - 2014/6/20

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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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Ablation of coactivator Med1 switches the cell fate of dental epithelia to that generating hair

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