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Cell Death Discov. 2018 Feb 9;4:14. doi: 10.1038/s41420-017-0014-5. eCollection 2018 Dec.

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

Author information

1
1Stem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology, Proteos, Singapore, Singapore.
2
2School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
3
3Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
4
4Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
5
5Microfluidics Systems Biology Laboratory, Institute of Molecular and Cell Biology, Proteos, Singapore, Singapore.
6
6Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore.
7
7Clinical Islet Laboratory, University of Alberta Hospital, Edmonton, AB, Canada.
8
8Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium, Helios, Singapore, Singapore.

Abstract

Human pancreatic islets containing insulin-secreting β-cells are notoriously heterogeneous in cell composition. Since β-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 β-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 β-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 β-cell functional decline once isolated. Therefore, stabilizing β-cell identity upon isolation may improve its functionality.

Conflict of interest statement

The authors declare that they have no competing interests.

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