Single Cell Transcriptome Analysis Reveals Pancreatic Hormone Lineage Decisions

Authors

• E Duvall
• C Benitez
• M Enge

Abstract

Recent work demonstrating lost or impaired beta cells in diabetes can be replaced with insulin producing cells, generated from renewable sources such as embryonic stem cells has sparked great excitement. However, the molecular and cellular processes leading to beta cell differentiation are not well understood. Single cell technologies hold the promise to address these challenges and accelerate the study of organ development and regenerative medicine approaches to replace damaged or diseased organs. Here we used single-cell RNA-Seq to analyze the transcriptomes of 495 embryonic mouse pancreatic cells (E15). We used established computational tools to study lineage decisions and identify differentially expressed genes between endocrine progenitors and distinct hormonal cell types (beta, alpha, delta). We found a previously unrecognized cell population, likely serving as transitional cells, prior to the expression of hormone specific genes. The diverging hormonal lineages show that alpha and delta cells are more similar than beta cells. We also identified a list of key transcription factors unique to these transitional cells, as well as alpha delta cell lineage and beta cell lineage. Our results demonstrate the feasibility of using single cell RNA sequencing (scRNA-seq) data obtained from embryonic mouse cells to derive insights into gene regulatory networks that define cell lineages.

Scientific Focus Area: Developmental Biology

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