Journal
STEM CELLS
Volume 41, Issue 6, Pages 643-657Publisher
OXFORD UNIV PRESS
DOI: 10.1093/stmcls/sxad030
Keywords
single-cell RNA sequencing; Sox17; endoderm; hepato-pancreato-biliary system; endothelium; hematopoiesis
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During early embryogenesis, the transcription factor SOX17 plays a role in the formation of the hepato-pancreato-biliary system and vascular-hematopoietic emergence. Using a dual-color temporal lineage-tracing strategy combined with single-cell RNA sequencing, researchers analyzed cells from Sox17-expressing lineages and identified distinct cellular clusters from all 3 germ layers. Differential gene expression analysis revealed specialized subtypes of endothelial cells and subsets of hepatic, pancreatic, and biliary progenitors within the posterior foregut endoderm.
During early embryogenesis, the transcription factor SOX17 contributes to hepato-pancreato-biliary system formation and vascular-hematopoietic emergence. To better understand Sox17 function in the developing endoderm and endothelium, we developed a dual-color temporal lineage-tracing strategy in mice combined with single-cell RNA sequencing to analyze 6934 cells from Sox17-expressing lineages at embryonic days 9.0-9.5. Our analyses showed 19 distinct cellular clusters combined from all 3 germ layers. Differential gene expression, trajectory and RNA-velocity analyses of endothelial cells revealed a heterogenous population of uncommitted and specialized endothelial subtypes, including 2 hemogenic populations that arise from different origins. Similarly, analyses of posterior foregut endoderm revealed subsets of hepatic, pancreatic, and biliary progenitors with overlapping developmental potency. Calculated gene-regulatory networks predict gene regulons that are dominated by cell type-specific transcription factors unique to each lineage. Vastly different Sox17 regulons found in endoderm versus endothelial cells support the differential interactions of SOX17 with other regulatory factors thereby enabling lineage-specific regulatory actions.
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