학술논문

Lineage dynamics of murine pancreatic development at single-cell resolution.
Document Type
article
Source
Nature communications. 9(1)
Subject
Pancreas
Epithelium
Cell Line
Mesoderm
Animals
Mice
Inbred C57BL
Mice
Transgenic
Humans
Microscopy
Fluorescence
In Situ Hybridization
Reverse Transcriptase Polymerase Chain Reaction
Cell Differentiation
Gene Expression Regulation
Developmental
Cell Lineage
Single-Cell Analysis
Human Embryonic Stem Cells
Language
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.