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.

中文翻译：

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在单细胞分辨率下鼠胰腺发育的谱系动力学。

器官发生需要多个细胞谱系之间复杂的相互作用，这些相互作用可以协调其随着时间的增长，分化和成熟。在这里，我们使用单细胞RNA测序，免疫荧光，原位杂交和遗传谱系追踪相结合的方法，对小鼠胰腺上皮和间质隔室内发育过程中的细胞类型进行了分析。我们确定以前低估的间充质细胞异质性，并重建胰腺上皮和间充质细胞类型之间潜在的谱系关系。在上皮细胞内，我们发现了以前未描述的内分泌祖细胞群，以及在人类胎儿组织和人类胚胎干细胞中向胰腺β细胞命运分化的类似种群。进一步，我们沿着该群体向着α或β细胞谱系的分化轨迹识别出候选的转录调节因子。这项工作建立了胰腺发育的路线图，并展示了这种方法在了解发育器官中谱系动力学方面的广泛用途。