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

Lineage dynamics of murine pancreatic development at single-cell resolution.
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DOI:
10.1038/s41467-018-06176-3
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发表时间:
2018-09-25
影响因子:
16.6
通讯作者:
Sneddon JB
Sneddon JB
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Byrnes LE;Wong DM;Subramaniam M;Meyer NP;Gilchrist CL;Knox SM;Tward AD;Ye CJ;Sneddon JB

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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.
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