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

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.

SUBMITTER: Yoshizaki K

PROVIDER: S-EPMC4065011 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Yoshizaki Keigo K Hu Lizhi L Nguyen Thai T Sakai Kiyoshi K He Bing B Fong Chak C Yamada Yoshihiko Y Bikle Daniel D DD Oda Yuko Y

PloS one 20140620 6

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 ep ...[more]

PMID: 24949995

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

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-09-23 | E-GEOD-50504 | biostudies-arrayexpress

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2013-09-23 | GSE50504 | GEO

Ablation of coactivator Med1 switches the cell fate of dental epithelia to that generating hair [mixed stage]

Project description:Cell fate is defined by specific transcriptional program. Here, we provide evidence that the transcriptional coactivator, Mediator 1 (MED1), is critical in determining the cell fate of ectodermal epithelia. MED1 ablation disrupted enamel formation and generated hair adjacent to the incisors. Deletion of MED1 altered the differentiation of dental epithelia to one expressing epidermal and hair genes similar to the skin. The cellular switch from dental to epidermal/hair lineage was characterized by abnormalities in MED1 deficient dental epithelial stem cells residing in cervical loop. MED1 deficiency caused a failure of dental epithelial stem cells to commit to the dental stratum intermedium regulated by Notch signaling. Instead, MED1 deficient cells retained stem cell potentials expressing Sox2. These cells were eventually adopted an epidermal fate probably through calcium provided through capillary networks, which is originally utilized for enamel formation. Our results demonstrate that MED1 regulates Sox2/Notch1 regulated cell lineage determination in dental epithelia. Our study also shows a potential to regenerate hairs by using genetically engineered dental tissues or cells outside of the skin. n=3 WT and KO (each sample contain dissected dental tissues from 3 mice combined)

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Ablation of coactivator Med1 switches the cell fate of dental epithelia to that generating hair [maturation stage]

Project description:Cell fate is defined by specific transcriptional program. Here, we provide evidence that the transcriptional coactivator, Mediator 1 (MED1), is critical in determining the cell fate of ectodermal epithelia. MED1 ablation disrupted enamel formation and generated hair adjacent to the incisors. Deletion of MED1 altered the differentiation of dental epithelia to one expressing epidermal and hair genes similar to the skin. The cellular switch from dental to epidermal/hair lineage was characterized by abnormalities in MED1 deficient dental epithelial stem cells residing in cervical loop. MED1 deficiency caused a failure of dental epithelial stem cells to commit to the dental stratum intermedium regulated by Notch signaling. Instead, MED1 deficient cells retained stem cell potentials expressing Sox2. These cells were eventually adopted an epidermal fate probably through calcium provided through capillary networks, which is originally utilized for enamel formation. Our results demonstrate that MED1 regulates Sox2/Notch1 regulated cell lineage determination in dental epithelia. Our study also shows a potential to regenerate hairs by using genetically engineered dental tissues or cells outside of the skin. n=4 WT and KO (each group contains dissected dental tissues from 3 mice combined)

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Ablation of coactivator Med1 switches the cell fate of dental epithelia to that generating hair [CL stage]

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Ablation of coactivator Med1 switches the cell fate of dental epithelia to that generating hair [CL stage]

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Coactivator MED1 ablation in keratinocytes results in hair-cycling defects and epidermal alterations.

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