ArticleProceedings of the National Academy of Sciences of the United States of America2019
Single-cell RNA-seq identifies a reversible mesodermal activation in abnormally specified epithelia of p63 EEC syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 34 citations in OpenAlex.
- p63 in skin homeostasis and disease: molecular mechanisms and therapeutic potentials.Cell death discovery · 2026Review
- p63: A Master Regulator at the Crossroads Between Development, Senescence, Aging, and Cancer.Cells · 2025Review
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- Single-cell RNA sequencing in oral science: Current awareness and perspectives.Cell proliferation · 2022Review
- Article
- Enhanced pro-apoptosis gene signature following the activation of TAp63α in oocytes upon γ irradiation.Cell death & disease · 2022Article
- CRISPR-Cas9‒Based Genomic Engineering in Keratinocytes: From Technology to Application.JID innovations : skin science from molecules to population health · 2022Review
- Differentiation of pluripotent stem cells for modeling human skin development and potential applications.Frontiers in cell and developmental biology · 2022Review
- Mouse models in palate development and orofacial cleft research: Understanding the crucial role and regulation of epithelial integrity in facial and palate morphogenesis.Current topics in developmental biology · 2022Article
- ANANSE: an enhancer network-based computational approach for predicting key transcription factors in cell fate determination.Nucleic acids research · 2021Article
- Lyophilized powder of mesenchymal stem cell supernatant attenuates acute lung injury through the IL-6-p-STAT3-p63-JAG2 pathway.Stem cell research & therapy · 2021Article
- hiPSC-Derived Epidermal Keratinocytes from Ichthyosis Patients Show Altered Expression of Cornification Markers.International journal of molecular sciences · 2021Article
- Isoform-Specific Roles of Mutant p63 in Human Diseases.Cancers · 2021Review
- TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development.Cellular and molecular life sciences : CMLS · 2020Review
- Identification of a Novel Variant ofBioMed research international · 2020Article
- p63 cooperates with CTCF to modulate chromatin architecture in skin keratinocytes.Epigenetics & chromatin · 2019Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in transcription factor p63 are associated with developmental disorders that manifest defects in stratified epithelia including the epidermis. The underlying cellular and molecular mechanism is however not yet understood. We established an epidermal commitment model using human induced pluripotent stem cells (iPSCs) and characterized differentiation defects of iPSCs derived from ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome patients carrying p63 mutations. Transcriptome analyses revealed stepwise cell fate transitions during epidermal commitment: Specification from multipotent simple epithelium to basal stratified epithelia and ultimately to the mature epidermal fate. Differentiation defects of EEC iPSCs caused by p63 mutations occurred during the specification switch from the simple epithelium to the basal-stratified epithelial fate. Single-cell transcriptome and pseudotime analyses of cell states identified mesodermal activation that was associated with the deviated commitment route of EEC iPSCs. Integrated analyses of differentially regulated genes and p63-dependent dynamic genomic enhancers during epidermal commitment suggest that p63 directly controls epidermal gene activation at the specification switch and has an indirect effect on mesodermal gene repression. Importantly, inhibitors of mesodermal induction enhanced epidermal commitment of EEC iPSCs. Our findings demonstrate that p63 is required for specification of stratified epithelia, and that epidermal commitment defects caused by p63 mutations can be reversed by repressing mesodermal induction. This study provides insights into disease mechanisms underlying stratified epithelial defects caused by p63 mutations and suggests potential therapeutic strategies for the disease.
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