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Lineage dynamics of murine pancreatic development at single-cell resolution
Organogenesis requires the complex interactions of multiple cell lineages that coordinate their expansion, differentiation, and maturation over time. Here, we profile the cell types within the epithelial and mesenchymal compartments of the murine pancreas across developmental time using a combinatio...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156586/ https://www.ncbi.nlm.nih.gov/pubmed/30254276 http://dx.doi.org/10.1038/s41467-018-06176-3 |
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author | Byrnes, Lauren E. Wong, Daniel M. Subramaniam, Meena Meyer, Nathaniel P. Gilchrist, Caroline L. Knox, Sarah M. Tward, Aaron D. Ye, Chun J. Sneddon, Julie B. |
author_facet | Byrnes, Lauren E. Wong, Daniel M. Subramaniam, Meena Meyer, Nathaniel P. Gilchrist, Caroline L. Knox, Sarah M. Tward, Aaron D. Ye, Chun J. Sneddon, Julie B. |
author_sort | Byrnes, Lauren E. |
collection | PubMed |
description | Organogenesis requires the complex interactions of multiple cell lineages that coordinate their expansion, differentiation, and maturation over time. Here, we profile the cell types within the epithelial and mesenchymal compartments of the murine pancreas across developmental time using a combination of single-cell RNA sequencing, immunofluorescence, in situ hybridization, and genetic lineage tracing. We identify previously underappreciated cellular heterogeneity of the developing mesenchyme and reconstruct potential lineage relationships among the pancreatic mesothelium and mesenchymal cell types. Within the epithelium, we find a previously undescribed endocrine progenitor population, as well as an analogous population in both human fetal tissue and human embryonic stem cells differentiating toward a pancreatic beta cell fate. Further, we identify candidate transcriptional regulators along the differentiation trajectory of this population toward the alpha or beta cell lineages. This work establishes a roadmap of pancreatic development and demonstrates the broad utility of this approach for understanding lineage dynamics in developing organs. |
format | Online Article Text |
id | pubmed-6156586 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61565862018-09-27 Lineage dynamics of murine pancreatic development at single-cell resolution Byrnes, Lauren E. Wong, Daniel M. Subramaniam, Meena Meyer, Nathaniel P. Gilchrist, Caroline L. Knox, Sarah M. Tward, Aaron D. Ye, Chun J. Sneddon, Julie B. Nat Commun Article Organogenesis requires the complex interactions of multiple cell lineages that coordinate their expansion, differentiation, and maturation over time. Here, we profile the cell types within the epithelial and mesenchymal compartments of the murine pancreas across developmental time using a combination of single-cell RNA sequencing, immunofluorescence, in situ hybridization, and genetic lineage tracing. We identify previously underappreciated cellular heterogeneity of the developing mesenchyme and reconstruct potential lineage relationships among the pancreatic mesothelium and mesenchymal cell types. Within the epithelium, we find a previously undescribed endocrine progenitor population, as well as an analogous population in both human fetal tissue and human embryonic stem cells differentiating toward a pancreatic beta cell fate. Further, we identify candidate transcriptional regulators along the differentiation trajectory of this population toward the alpha or beta cell lineages. This work establishes a roadmap of pancreatic development and demonstrates the broad utility of this approach for understanding lineage dynamics in developing organs. Nature Publishing Group UK 2018-09-25 /pmc/articles/PMC6156586/ /pubmed/30254276 http://dx.doi.org/10.1038/s41467-018-06176-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Byrnes, Lauren E. Wong, Daniel M. Subramaniam, Meena Meyer, Nathaniel P. Gilchrist, Caroline L. Knox, Sarah M. Tward, Aaron D. Ye, Chun J. Sneddon, Julie B. Lineage dynamics of murine pancreatic development at single-cell resolution |
title | Lineage dynamics of murine pancreatic development at single-cell resolution |
title_full | Lineage dynamics of murine pancreatic development at single-cell resolution |
title_fullStr | Lineage dynamics of murine pancreatic development at single-cell resolution |
title_full_unstemmed | Lineage dynamics of murine pancreatic development at single-cell resolution |
title_short | Lineage dynamics of murine pancreatic development at single-cell resolution |
title_sort | lineage dynamics of murine pancreatic development at single-cell resolution |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156586/ https://www.ncbi.nlm.nih.gov/pubmed/30254276 http://dx.doi.org/10.1038/s41467-018-06176-3 |
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