Lineage dynamics of murine pancreatic development at single-cell resolution

• Published in: Nature communications Vol. 9; no. 1; pp. 3922 - 17
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.09.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/100; 13/106; 13/31; 13/51; 14; 14/19; 14/32; 14/63; 38; 38/77; 45; 45/91; 631/136/142; 631/208/199; 692/698/2741/416; Animals; Beta cells; Cell Differentiation - genetics; Cell fate; Cell Line; Cell Lineage - genetics; Differentiation; Embryo cells; Embryos; Epithelium; Epithelium - embryology; Epithelium - metabolism; Fetuses; Gene Expression Regulation, Developmental; Gene sequencing; Heterogeneity; Human Embryonic Stem Cells - cytology; Human Embryonic Stem Cells - metabolism; Humanities and Social Sciences; Humans; Immunofluorescence; In Situ Hybridization; Mesenchyme; Mesoderm - cytology; Mesoderm - embryology; Mesoderm - metabolism; Mesothelium; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Fluorescence; multidisciplinary; Organogenesis; Organs; Pancreas; Pancreas - cytology; Pancreas - embryology; Pancreas - metabolism; Regulators; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Single-Cell Analysis - methods; Stem cell transplantation; Stem cells; Transcription
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-06176-3

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. Coordinated proliferation and differentiation of diverse cell populations drive pancreatic epithelial and mesenchymal development. Here, the authors profile cell type dynamics in the developing mouse pancreas using single-cell RNA sequencing, identifying mesenchymal subtypes and undescribed endocrine progenitors.