scholarly journals Single-cell RNA-seq identifies a reversible mesodermal activation in abnormally specified epithelia of p63 EEC syndrome

2019 ◽  
Vol 116 (35) ◽  
pp. 17361-17370 ◽  
Author(s):  
Eduardo Soares ◽  
Quan Xu ◽  
Qingqing Li ◽  
Jieqiong Qu ◽  
Yuxuan Zheng ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Developmental Disorders ◽  
Cleft Lip ◽  
Gene Activation ◽  
Eec Syndrome ◽  
Cleft Lip Palate ◽  
Induced Pluripotent ◽  
Cell Transcriptome ◽  
Stratified Epithelia

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.

scholarly journals Single-cell RNA-seq identifies a reversible epithelial-mesenchymal transition in abnormally specified epithelia of p63 EEC syndrome

2018 ◽  
Author(s):  
Eduardo Soares ◽  
Quan Xu ◽  
Qingqing Li ◽  
Jieqiong Qu ◽  
Yuxuan Zheng ◽  
...  
Keyword(s):  
Cell Fate ◽  
Developmental Disorders ◽  
Cleft Lip ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Disease Mechanisms ◽  
Eec Syndrome ◽  
Cleft Lip Palate ◽  
Induced Pluripotent ◽  
Stratified Epithelia

AbstractMutations 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 distinct step-wise cell fate transitions during epidermal commitment; from multipotent simple epithelium to basal stratified epithelia, and ultimately to the mature epidermal fate. Differentiation defects of EEC iPSCs caused by mutant p63 occurred during the specification switch from the simple epithelium to the basal stratified epithelial fate. Single-cell transcriptome and pseudotime analyses identified signatures of embryonic epithelial-mesenchymal transition (EMT) associated with the deviated commitment route of EEC iPSCs. Repressing mesodermal activation reversed the EMT and enhanced epidermal commitment. Our findings demonstrate that p63 is required for specification of stratified epithelia, probably by repressing embryonic EMT during epidermal commitment. This study provides insights into disease mechanisms underlying stratified epithelial defects caused by p63 mutations and suggests potential therapeutic strategies for the disease.Significance statementMutations in p63 cause several developmental disorders with defects of epithelial related organs and tissues including the epidermis. Our study is to dissect the unknown cellular and molecular pathomechanism. We utilized human induced pluripotent stem cells (iPSCs) derived from ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome patients carrying p63 mutations and studied transcriptome changes during differentiation of these cells to epidermal cells. Our analyses showed that the specification of the proper epithelial cell fate was affected by p63 EEC mutations, with an abnormal embryonic epithelial-mesenchymal transition (EMT). Repressing mesodermal activation reversed the EMT and enhanced epidermal commitment. This study provides insights into disease mechanisms associated with p63 mutations and suggests potential therapeutic strategies.

scholarly journals Prenatal Diagnosis of EEC Syndrome with “Lobster Claw” Anomaly by 3D Ultrasound

2012 ◽  
Vol 2 ◽  
pp. 40 ◽  
Author(s):  
Livia T. Rios ◽  
Edward Araujo ◽  
Ana C. R. Caetano ◽  
Luciano M. Nardozza ◽  
Antonio F. Moron ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Cleft Lip ◽  
Three Dimensional ◽  
3D Ultrasound ◽  
Eec Syndrome ◽  
Cleft Lip Palate ◽  
The Right ◽  
Hands And Feet ◽  
Genetic Anomaly ◽  
Better Than

The EEC syndrome is a genetic anomaly characterized by the triad: ectodermal dysplasia (development of anomalies of the structures derived from the embryonic ectodermal layer), ectrodactyly (extremities, hands and feet malformations) and cleft lip and/or palate; these malformations can be seen together or in isolation. The prenatal diagnosis can be made by two-dimensional ultrasonography (2DUS) that identifies the facial and/or limb anomalies, most characteristic being the “lobster-claw” hands. The three-dimensional ultrasonography (3DUS) provides a better analysis of the malformations than the 2DUS. A 25-year-old primigravida, had her first transvaginal ultrasonography that showed an unique fetus with crow-rump length of 47 mm with poorly defined hands and feet,. She was suspected of having sporadic form of EEC syndrome. The 2DUS performed at 19 weeks confirmed the EEC syndrome, showing a fetus with lobster-claw hands (absence of the 2nd and 3rd fingers), left foot with the absence of the 3rd toe and the right foot with syndactyly, and presence of cleft lip/palate. The 3DUS defined the anomalies much better than 2DUS including the lobster-claw hands.

scholarly journals A novel c.1037C > G (p.Ala346Gly) mutation in TP63 as cause of the ectrodactyly-ectodermal dysplasia and cleft lip/palate (EEC) syndrome

2015 ◽  
Vol 38 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Leandro Ucela Alves ◽  
Eliete Pardono ◽  
Paulo A. Otto ◽  
Regina Célia Mingroni Netto
Keyword(s):  
Cleft Lip ◽  
Ectodermal Dysplasia ◽  
Eec Syndrome ◽  
Cleft Lip Palate

scholarly journals Lifelong single-cell profiling of cranial neural crest diversification

2021 ◽  
Author(s):  
Peter Fabian ◽  
Kuo-Chang Tseng ◽  
Mathi Thiruppathy ◽  
Claire Arata ◽  
Hung-Jhen Chen ◽  
...  
Keyword(s):  
Neural Crest ◽  
Single Cell ◽  
Cell Fate ◽  
Intrinsic Property ◽  
Chromatin Accessibility ◽  
Specific Cell ◽  
List Type ◽  
Cranial Neural Crest ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

AbstractThe cranial neural crest generates a huge diversity of derivatives, including the bulk of connective and skeletal tissues of the vertebrate head. How neural crest cells acquire such extraordinary lineage potential remains unresolved. By integrating single-cell transcriptome and chromatin accessibility profiles of cranial neural crest-derived cells across the zebrafish lifetime, we observe region-specific establishment of enhancer accessibility for distinct fates. Neural crest-derived cells rapidly diversify into specialized progenitors, including multipotent skeletal progenitors, stromal cells with a regenerative signature, fibroblasts with a unique metabolic signature linked to skeletal integrity, and gill-specific progenitors generating cell types for respiration. By retrogradely mapping the emergence of lineage-specific chromatin accessibility, we identify a wealth of candidate lineage-priming factors, including a Gata3 regulatory circuit for respiratory cell fates. Rather than multilineage potential being an intrinsic property of cranial neural crest, our findings support progressive and region-specific chromatin remodeling underlying acquisition of diverse neural crest lineage potential.HighlightsSingle-cell transcriptome and chromatin atlas of cranial neural crestProgressive emergence of region-specific cell fate competencyChromatin accessibility mapping identifies candidate lineage regulatorsGata3 function linked to gill-specific respiratory programGraphical Abstract

The case of prenatal ultrasound diagnosis of EEC syndrome (Ectrodactyly, Ectodermal dysplasia, Cleft lip/palate syndrome) at 14 weeks of gestation

2019 ◽  
Author(s):  
I.V. Andrusenko
Keyword(s):  
Cleft Lip ◽  
Ectodermal Dysplasia ◽  
Prenatal Ultrasound ◽  
Ultrasound Diagnosis ◽  
Eec Syndrome ◽  
Cleft Lip Palate

Case of prenatal ultrasound diagnosis of EEC syndrome at 14 weeks of gestation is presented. A rare feature of the case was the ectrodactyly of all limbs.

Ectrodactyly ectodermal dysplasia cleft lip/palate (EEC) syndrome in a family

2014 ◽  
Vol 0 (0) ◽  
Author(s):  
Anil Kumar Gaur ◽  
Rajendra Sharma ◽  
Amit Subhash Mhambre ◽  
Sudhir Mishra
Keyword(s):  
Cleft Lip ◽  
Ectodermal Dysplasia ◽  
Eec Syndrome ◽  
Cleft Lip Palate
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