Single-cell analyses of human islet cells reveal de-differentiation signatures

Abstract

Human pancreatic islets containing insulin-secreting ?-cells are notoriously heterogeneous in cell composition. Since ?-cell failure is the root cause of diabetes, understanding this heterogeneity is of paramount importance. Recent reports have cataloged human islet transcriptome but not compared single ?-cells in detail. Here, we scrutinized ex vivo human islet cells from healthy donors and show that they exhibit de-differentiation signatures. Using single-cell gene expression and immunostaining analyses, we found healthy islet cells to contain polyhormonal transcripts, and INS+ cells to express decreased levels of ?-cell genes but high levels of progenitor markers. Rare cells that are doubly positive for progenitor markers/exocrine signatures, and endocrine/exocrine hormones were also present. We conclude that ex vivo human islet cells are plastic and can possibly de-/trans-differentiate across pancreatic cell fates, partly accounting for ?-cell functional decline once isolated. Therefore, stabilizing ?-cell identity upon isolation may improve its functionality. © 2018, The Author(s).