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Nat Commun. 2018 Sep 25;9(1):3922. doi: 10.1038/s41467-018-06176-3.

Lineage dynamics of murine pancreatic development at single-cell resolution.

Author information

1
Diabetes Center, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA, 94143, USA.
2
Institute for Human Genetics, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA, 94143, USA.
3
Department of Cell and Tissue Biology, University of California, San Francisco, 513 Parnassus Avenue, CA, 94143, USA.
4
Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, 513 Parnassus Avenue, CA, 94143, USA.
5
Diabetes Center, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA, 94143, USA. julie.sneddon@ucsf.edu.

Abstract

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.

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