Single cell transcriptomic profiling of mouse pancreatic progenitors

Diana E Stanescu, Reynold Yu, Kyoung-Jae Won, Doris A Stoffers

17 Citationer (Scopus)

Abstract

The heterogeneity of the developing pancreatic epithelium and low abundance of endocrine progenitors limit the information derived from traditional expression studies. To identify genes that characterize early developmental tissues composed of multiple progenitor lineages, we applied single-cell RNA-Seq to embryonic day (e)13.5 mouse pancreata and performed integrative analysis with single cell data from mature pancreas. We identified subpopulations expressing macrophage or endothelial markers and new pancreatic progenitor markers. We also identified potential α-cell precursors expressing glucagon (Gcg) among the e13.5 pancreatic cells. Despite their high Gcg expression levels, these cells shared greater transcriptomic similarity with other e13.5 cells than with adult α-cells, indicating their immaturity. Comparative analysis identified the sodium-dependent neutral amino acid transporter, Slc38a5, as a characteristic gene expressed in α-cell precursors but not mature cells. By immunofluorescence analysis, we observed SLC38A5 expression in pancreatic progenitors, including in a subset of NEUROG3+ endocrine progenitors and MAFB+ cells and in all GCG+ cells. Expression declined in α-cells during late gestation and was absent in the adult islet. Our results suggest SLC38A5 as an early marker of α-cell lineage commitment.

OriginalsprogEngelsk
TidsskriftPhysiological Genomics
Vol/bind49
Udgave nummer2
Sider (fra-til)105-114
Antal sider10
ISSN1094-8341
DOI
StatusUdgivet - 14 feb. 2017
Udgivet eksterntJa

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