Similar Datasets
Project description:Effects of MED1 knock out on dental epithelia
| PRJNA971193 | ENA
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)
2013-09-23 | E-GEOD-50503 | biostudies-arrayexpress
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)
2013-09-23 | E-GEOD-50502 | biostudies-arrayexpress
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)
2013-09-23 | E-GEOD-50501 | biostudies-arrayexpress
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.
2013-09-23 | GSE50503 | GEO
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.
2013-09-23 | GSE50502 | GEO
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.
2013-09-23 | GSE50501 | GEO
Project description:Cell fates are defined by specific transcriptional program. We developed a mouse model, in which transcriptional program for ectoderm cell fate is altered in tooth and skin. Previously, we showed that genomic deletion of one subunit of Mediator complex, Mediator 1 (Med1) in vivo regenerate ectopic hair in incisors by disrupting Notch mediated enamel epithelial differentiation. However, precise process and molecular mechanism to induce epidermal fate are not clear. Med1 deficient dental epithelial stem cells exerts transcriptional program for skin epithelia reminiscent of the pattern in the skin. Epidermal transcripts were first induced prior to hair genes during dental epithelial differentiation, resemble to the pattern of embryonic developmental process of the skin. Hair genes was specifically induced at the anagen stage synchronized with hair cycling in the skin. Epidermal program was also induced in cultured adult stem cells called dental epithelial stem cell (DESC) that is derived from micro-dissected Med1 KO cervical loop tissues that are essential for continuous regeneration of mouse incisors. Gene expression profiles for the primary DESC with colony forming capability revealed that Med1 deletion suppressed Tgfb signaling by reducing the expression of ligands (Tgfb1, Inhibin ba), receptors and their extracellular targets such as Ctgf. Med1 deletion also induced Tgfb regulated reprogramming transcription factor, Klf4 that also known to drive transcription for epidermal genes. TGFb signaling was also suppressed in Med1 null epidermis in skin, in which epidermal fate was induced in hair follicle keratinocytes. Med1 silencing blocked expression of TGFb1 and suppressed both basal and recombinant TGFb induced Smad2/3 mediated transcription of TGFb target genes in vitro. These results demonstrate that Med1 deletion enhances epidermal transcriptional program in adult stem cells through regulation of TGFb signaling.
2018-12-31 | GSE112884 | GEO
Project description:Transcriptional profiling of Bmi1 mutant dental epithelia including the stem cell compartment to determine which genes are upregulated in response to loss of Bmi1. Two condition experiment: dental epithelia homozygous null for Bmi1 and WT dental epithelia. 4 replicates each
2013-04-12 | E-GEOD-45999 | biostudies-arrayexpress
Project description:Postnatal cell fate has been postulated to be primarily determined by the local tissue microenvironment. Here, we found that Mediator 1 (Med1) dependent epigenetic mechanisms dictate tissue-specific lineage commitment and progression of dental epithelia. Deletion of Med1, a key component of the Mediator complex linking enhancer activities to gene transcription, provokes a tissue extrinsic lineage shift, causing hair generation in the dental environment. Med1 deficiency gives rise to unusual hair growth via primitive cellular aggregates on incisors. Mechanistically, we found that Med1 establishes super-enhancers that control enamel lineage transcription factors in dental stem cells and their progenies. However, Med1 deficiency reshapes the enhancer landscapes and causes a switch from the dental epithelial transcriptional program towards hair and epidermis on incisors in vivo, and in dental epithelial stem cells in vitro. Med1 loss also provokes an increase in the number and size of enhancers. Interestingly, control dental epithelia already exhibit enhancers for hair and epidermal key transcription factors; these expand in size and transform into super-enhancers upon Med1 loss suggesting that these epigenetic mechanisms cause the transcriptomic and phenotypic shift towards epidermal and hair lineages. Thus, we propose a role for Med1 in safeguarding lineage specific enhancers, highlight the central role of enhancer accessibility and usage in lineage reprogramming and provide new insights into ectodermal regeneration. Duplicate Chip-seq for dental tisses from head region of cervical loop (CLH) containing dental epithelial stem cells and tail region (CLT) including progenies that were dissected from mandible of 4 week old conditional Krt14CreMed1 knockout (cKO) mice or littermate control (Ctrl) mice. Chip-seq was conducted by using antibodies against Mediator 1 (Med1) and H3K27ac (H3).
2023-06-22 | GSE221565 | GEO