Cell Type- and Tissue-specific Enhancers in Craniofacial Development
Cell Type- and Tissue-specific Enhancers in Craniofacial Development
Abstract The genetic basis of craniofacial birth defects and general variation in human facial shape remains poorly understood. Distant-acting transcriptional enhancers are a major category of non-coding genome function and have been shown to control the fine-tuned spatiotemporal expression of genes during critical stages of craniofacial development1–3. However, a lack of accurate maps of the genomic location and cell type-specific in vivo activities of all craniofacial enhancers prevents their systematic exploration in human genetics studies. Here, we combined histone modification and chromatin accessibility profiling from different stages of human craniofacial development with single-cell analyses of the developing mouse face to create a comprehensive catalogue of the regulatory landscape of facial development at tissue- and single cell-resolution. In total, we identified approximately 14,000 enhancers across seven developmental stages from weeks 4 through 8 of human embryonic face development. We used transgenic mouse reporter assays to determine the in vivo activity patterns of human face enhancers predicted from these data. Across 16 in vivo validated human enhancers, we observed a rich diversity of craniofacial subregions in which these enhancers are active in vivo. To annotate the cell type specificities of human-mouse conserved enhancers, we performed single-cell RNA-seq and single-nucleus ATAC-seq of mouse craniofacial tissues from embryonic days e11.5 to e15.5. By integrating these data across species, we find that the majority (56%) of human craniofacial enhancers are functionally conserved in mice, providing cell type- and embryonic stage-resolved predictions of their in vivo activity profiles. Using retrospective analysis of known craniofacial enhancers in combination with single cell-resolved transgenic reporter assays, we demonstrate the utility of these data for predicting the in vivo cell type specificity of enhancers. Taken together, our data provide an expansive resource for genetic and developmental studies of human craniofacial development. Graphical Abstractbiorxiv;2023.06.26.546603v1/UFIG1F1ufig1
Fukuda-Yuzawa Yoko、Plajzer-Frick Ingrid、Kato Momoe、Hunter Riana D.、von Maydell Kianna、Wang Allen、Lisgo Steven、Dickel Diane E.、Visel Axel、Blow Matthew J.、Akiyama Jennifer A.、Paraiso Kitt、Kosicki Michael、Osterwalder Marco、Zhu Yiwen、Kelman Guy、Spurrell Cailyn H.、Ren Bing、Pennacchio Len A.、Afzal Sarah Yasmeen、Amaral Maria Luisa、Rajderkar Sudha Sunil、Cook Laura E.、Darbellay Fabrice、Wu Han、Barozzi Iros、Lin Lin、Novak Catherine S.、Preissl Sebastian、Tran Stella、Afzal Veena
Environmental Genomics & System Biology Division, Lawrence Berkeley National Laboratory||University Research Management Center, Tohoku UniversityEnvironmental Genomics & System Biology Division, Lawrence Berkeley National LaboratoryEnvironmental Genomics & System Biology Division, Lawrence Berkeley National LaboratoryEnvironmental Genomics & System Biology Division, Lawrence Berkeley National Laboratory||UC San Francisco, Division of Experimental MedicineEnvironmental Genomics & System Biology Division, Lawrence Berkeley National LaboratoryCenter for Epigenomics, University of California San Diego School of MedicineHuman Developmental Biology Resource, Institute of Genetic Medicine, Newcastle University||Newcastle University Biosciences Institute, Faculty of Medical Sciences, Newcastle UniversityEnvironmental Genomics & System Biology Division, Lawrence Berkeley National Laboratory||Octant Inc.Environmental Genomics & System Biology Division, Lawrence Berkeley National Laboratory||U.S. Department of Energy Joint Genome Institute||School of Natural Sciences, University of CaliforniaU.S. Department of Energy Joint Genome InstituteEnvironmental Genomics & System Biology Division, Lawrence Berkeley National LaboratoryEnvironmental Genomics & System Biology Division, Lawrence Berkeley National LaboratoryEnvironmental Genomics & System Biology Division, Lawrence Berkeley National LaboratoryEnvironmental Genomics & System Biology Division, Lawrence Berkeley National Laboratory||Department for BioMedical Research, University of BernEnvironmental Genomics & System Biology Division, Lawrence Berkeley National LaboratoryEnvironmental Genomics & System Biology Division, Lawrence Berkeley National Laboratory||The Jerusalem Center for Personalized Computational Medicine, Hebrew University of JerusalemEnvironmental Genomics & System Biology Division, Lawrence Berkeley National LaboratoryInstitute of Genome Medicine, Moores Cancer Center, University of California, San Diego School of MedicineEnvironmental Genomics & System Biology Division, Lawrence Berkeley National Laboratory||U.S. Department of Energy Joint Genome Institute||Comparative Biochemistry Program, University of CaliforniaEnvironmental Genomics & System Biology Division, Lawrence Berkeley National Laboratory||Lucile Packard Children?ˉs Hospital, Stanford UniversityBioinformatics and Systems Biology Graduate Program, University of California San DiegoEnvironmental Genomics & System Biology Division, Lawrence Berkeley National LaboratoryEnvironmental Genomics & System Biology Division, Lawrence Berkeley National LaboratoryEnvironmental Genomics & System Biology Division, Lawrence Berkeley National Laboratory||Department of Genetic Medicine and Development, Faculty of Medicine, University of GenevaEnvironmental Genomics & System Biology Division, Lawrence Berkeley National LaboratoryEnvironmental Genomics & System Biology Division, Lawrence Berkeley National Laboratory||Center for Cancer Research, Medical University of Vienna||Department of Surgery and Cancer, Imperial College LondonCenter for Epigenomics, University of California San Diego School of MedicineEnvironmental Genomics & System Biology Division, Lawrence Berkeley National LaboratoryCenter for Epigenomics, University of California San Diego School of Medicine||Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of FreiburgEnvironmental Genomics & System Biology Division, Lawrence Berkeley National LaboratoryEnvironmental Genomics & System Biology Division, Lawrence Berkeley National Laboratory
遗传学细胞生物学分子生物学
Fukuda-Yuzawa Yoko,Plajzer-Frick Ingrid,Kato Momoe,Hunter Riana D.,von Maydell Kianna,Wang Allen,Lisgo Steven,Dickel Diane E.,Visel Axel,Blow Matthew J.,Akiyama Jennifer A.,Paraiso Kitt,Kosicki Michael,Osterwalder Marco,Zhu Yiwen,Kelman Guy,Spurrell Cailyn H.,Ren Bing,Pennacchio Len A.,Afzal Sarah Yasmeen,Amaral Maria Luisa,Rajderkar Sudha Sunil,Cook Laura E.,Darbellay Fabrice,Wu Han,Barozzi Iros,Lin Lin,Novak Catherine S.,Preissl Sebastian,Tran Stella,Afzal Veena.Cell Type- and Tissue-specific Enhancers in Craniofacial Development[EB/OL].(2025-03-28)[2025-05-16].https://www.biorxiv.org/content/10.1101/2023.06.26.546603.点此复制
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