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Cell Type- and Tissue-specific Enhancers in Craniofacial Development
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 c...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327103/ https://www.ncbi.nlm.nih.gov/pubmed/37425964 http://dx.doi.org/10.1101/2023.06.26.546603 |
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author | Rajderkar, Sudha Sunil Paraiso, Kitt Amaral, Maria Luisa Kosicki, Michael Cook, Laura E. Darbellay, Fabrice Spurrell, Cailyn H. Osterwalder, Marco Zhu, Yiwen Wu, Han Afzal, Sarah Yasmeen Blow, Matthew J. Kelman, Guy Barozzi, Iros Fukuda-Yuzawa, Yoko Akiyama, Jennifer A. Afzal, Veena Tran, Stella Plajzer-Frick, Ingrid Novak, Catherine S. Kato, Momoe Hunter, Riana D. von Maydell, Kianna Wang, Allen Lin, Lin Preissl, Sebastian Lisgo, Steven Ren, Bing Dickel, Diane E. Pennacchio, Len A. Visel, Axel |
author_facet | Rajderkar, Sudha Sunil Paraiso, Kitt Amaral, Maria Luisa Kosicki, Michael Cook, Laura E. Darbellay, Fabrice Spurrell, Cailyn H. Osterwalder, Marco Zhu, Yiwen Wu, Han Afzal, Sarah Yasmeen Blow, Matthew J. Kelman, Guy Barozzi, Iros Fukuda-Yuzawa, Yoko Akiyama, Jennifer A. Afzal, Veena Tran, Stella Plajzer-Frick, Ingrid Novak, Catherine S. Kato, Momoe Hunter, Riana D. von Maydell, Kianna Wang, Allen Lin, Lin Preissl, Sebastian Lisgo, Steven Ren, Bing Dickel, Diane E. Pennacchio, Len A. Visel, Axel |
author_sort | Rajderkar, Sudha Sunil |
collection | PubMed |
description | 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 development(1–3). 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. |
format | Online Article Text |
id | pubmed-10327103 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-103271032023-07-08 Cell Type- and Tissue-specific Enhancers in Craniofacial Development Rajderkar, Sudha Sunil Paraiso, Kitt Amaral, Maria Luisa Kosicki, Michael Cook, Laura E. Darbellay, Fabrice Spurrell, Cailyn H. Osterwalder, Marco Zhu, Yiwen Wu, Han Afzal, Sarah Yasmeen Blow, Matthew J. Kelman, Guy Barozzi, Iros Fukuda-Yuzawa, Yoko Akiyama, Jennifer A. Afzal, Veena Tran, Stella Plajzer-Frick, Ingrid Novak, Catherine S. Kato, Momoe Hunter, Riana D. von Maydell, Kianna Wang, Allen Lin, Lin Preissl, Sebastian Lisgo, Steven Ren, Bing Dickel, Diane E. Pennacchio, Len A. Visel, Axel bioRxiv Article 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 development(1–3). 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. Cold Spring Harbor Laboratory 2023-06-26 /pmc/articles/PMC10327103/ /pubmed/37425964 http://dx.doi.org/10.1101/2023.06.26.546603 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Rajderkar, Sudha Sunil Paraiso, Kitt Amaral, Maria Luisa Kosicki, Michael Cook, Laura E. Darbellay, Fabrice Spurrell, Cailyn H. Osterwalder, Marco Zhu, Yiwen Wu, Han Afzal, Sarah Yasmeen Blow, Matthew J. Kelman, Guy Barozzi, Iros Fukuda-Yuzawa, Yoko Akiyama, Jennifer A. Afzal, Veena Tran, Stella Plajzer-Frick, Ingrid Novak, Catherine S. Kato, Momoe Hunter, Riana D. von Maydell, Kianna Wang, Allen Lin, Lin Preissl, Sebastian Lisgo, Steven Ren, Bing Dickel, Diane E. Pennacchio, Len A. Visel, Axel Cell Type- and Tissue-specific Enhancers in Craniofacial Development |
title | Cell Type- and Tissue-specific Enhancers in Craniofacial Development |
title_full | Cell Type- and Tissue-specific Enhancers in Craniofacial Development |
title_fullStr | Cell Type- and Tissue-specific Enhancers in Craniofacial Development |
title_full_unstemmed | Cell Type- and Tissue-specific Enhancers in Craniofacial Development |
title_short | Cell Type- and Tissue-specific Enhancers in Craniofacial Development |
title_sort | cell type- and tissue-specific enhancers in craniofacial development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327103/ https://www.ncbi.nlm.nih.gov/pubmed/37425964 http://dx.doi.org/10.1101/2023.06.26.546603 |
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