Project description:Induced pluripotent stem cells (iPSC) were generated from two patients affected by ankyloblepharon ectodermal dysplasia and clefting (AEC), an ectodermal dysplasia caused by mutations in TP63. The two TP63mutations(I537T and R598L) were corrected using Crispr/Cas9- mediated homologous recombination. The resulting conisogenic iPSC pairs were differentiated into keratinocytes and subjected to RNA-sequencing.
2018-01-16 | GSE109185 | GEO
Project description:Whole Exome Sequencing of Czech Dysplasia in a Chinese pedigree
| PRJNA1028766 | ENA
Project description:Whole exome sequencing for a patient with ectodermal dysplasia and dysgammaglobulinemia
Project description:Vertebrate Hox genes are key players in the establishment of structures during the development of the main body axis. Subsequently, they play important roles either in organizing secondary axial structures such as the appendages, or during homeostasis in postnatal stages and adulthood. Here we set up to analyze their elusive function in the ectodermal compartment, using the mouse limb bud as a model. We report that the HoxC gene cluster was globally co-opted to be transcribed in the distal limb ectoderm, where it is activated following the rule of temporal colinearity. These ectodermal cells subsequently produce various keratinized organs such as nails or claws. Accordingly, deletion of the HoxC cluster led to mice lacking nails (anonychia) and also hairs (alopecia), a condition stronger than the previously reported loss of function of Hoxc13, which is causative of the ectodermal dysplasia 9 (ECTD9) syndrome in human patients. We further identified, in mammals only, two ectodermal-specific enhancers located upstream the gene cluster, which act synergistically to regulate Hoxc genes in these ectodermal organs. Deletion of these enhancers alone or in combination revealed a strong quantitative component in the regulation of these genes in the ectoderm, suggesting that these two enhancers may have evolved along with mammals to provide the level of HOXC proteins necessary for the full development of hairs and nails.
Project description:Vertebrate Hox genes are key players in the establishment of structures during the development of the main body axis. Subsequently, they play important roles either in organizing secondary axial structures such as the appendages, or during homeostasis in postnatal stages and adulthood. Here we set up to analyze their elusive function in the ectodermal compartment, using the mouse limb bud as a model. We report that the HoxC gene cluster was globally co-opted to be transcribed in the distal limb ectoderm, where it is activated following the rule of temporal colinearity. These ectodermal cells subsequently produce various keratinized organs such as nails or claws. Accordingly, deletion of the HoxC cluster led to mice lacking nails (anonychia) and also hairs (alopecia), a condition stronger than the previously reported loss of function of Hoxc13, which is causative of the ectodermal dysplasia 9 (ECTD9) syndrome in human patients. We further identified, in mammals only, two ectodermal-specific enhancers located upstream the gene cluster, which act synergistically to regulate Hoxc genes in these ectodermal organs. Deletion of these enhancers alone or in combination revealed a strong quantitative component in the regulation of these genes in the ectoderm, suggesting that these two enhancers may have evolved along with mammals to provide the level of HOXC proteins necessary for the full development of hairs and nails.
Project description:Proper development of surface epithelium (SE) is a requisite for the normal development and function of ectodermal appendages; however, the molecular mechanisms underlying SE commitment remain largely unexplored. Here, we developed a KRT8 reporter system and utilized it to identify FOXO4 and SP6 as novel, essential regulators governing SE commitment. We found that the FOXO4-SP6 axis governs SE fate and its abrogation markedly impedes SE fate determination. Mechanistically, FOXO4 regulates SE initiation by shaping the SE chromatin accessibility landscape and regulating the deposition of H3K4me3. SP6, as a novel effector of FOXO4, activated SE-specific genes through modulating the H3K27ac deposition across their super enhancers. Our work highlights the regulatory function of the FOXO4-SP6 axis in SE development, contributing to an improved understanding of SE fate decisions and providing a research foundation for the therapeutic application of ectodermal dysplasia.