TY - JOUR
T1 - A transcriptomic roadmap to α- and β-cell differentiation in the embryonic pancreas
AU - van Gurp, Léon
AU - Muraro, Mauro J
AU - Dielen, Tim
AU - Seneby, Lina
AU - Dharmadhikari, Gitanjali
AU - Gradwohl, Gerard
AU - van Oudenaarden, Alexander
AU - de Koning, Eelco J P
N1 - © 2019. Published by The Company of Biologists Ltd.
PY - 2019/6/24
Y1 - 2019/6/24
N2 - During pancreatic development, endocrine cells appear from the pancreatic epithelium when Neurog3-positive cells delaminate and differentiate into α-, β-, γ- and δ-cells. The mechanisms involved in this process are still incompletely understood. We characterized the temporal, lineage-specific developmental programs during pancreatic development by sequencing the transcriptome of thousands of individual pancreatic cells from E12.5 to E18.5 in mice, and identified all known cell types that are present in the embryonic pancreas, but focused specifically on α- and β-cell differentiation by enrichment of a MIP-GFP reporter. We characterized transcriptomic heterogeneity in the tip domain based on proliferation, and characterized two endocrine precursor clusters marked by expression of Neurog3 and Fev Pseudotime analysis revealed specific branches for developing α- and β-cells, which allowed identification of specific gene regulation patterns. These include some known and many previously unreported genes that appear to define pancreatic cell fate transitions. This resource allows dynamic profiling of embryonic pancreas development at single cell resolution and reveals novel gene signatures during pancreatic differentiation into α- and β-cells.
AB - During pancreatic development, endocrine cells appear from the pancreatic epithelium when Neurog3-positive cells delaminate and differentiate into α-, β-, γ- and δ-cells. The mechanisms involved in this process are still incompletely understood. We characterized the temporal, lineage-specific developmental programs during pancreatic development by sequencing the transcriptome of thousands of individual pancreatic cells from E12.5 to E18.5 in mice, and identified all known cell types that are present in the embryonic pancreas, but focused specifically on α- and β-cell differentiation by enrichment of a MIP-GFP reporter. We characterized transcriptomic heterogeneity in the tip domain based on proliferation, and characterized two endocrine precursor clusters marked by expression of Neurog3 and Fev Pseudotime analysis revealed specific branches for developing α- and β-cells, which allowed identification of specific gene regulation patterns. These include some known and many previously unreported genes that appear to define pancreatic cell fate transitions. This resource allows dynamic profiling of embryonic pancreas development at single cell resolution and reveals novel gene signatures during pancreatic differentiation into α- and β-cells.
U2 - 10.1242/dev.173716
DO - 10.1242/dev.173716
M3 - Article
C2 - 31160419
SN - 0950-1991
VL - 146
JO - Development (Cambridge)
JF - Development (Cambridge)
IS - 12
ER -