Research Resource: Genetic Labeling of Human Islet Alpha Cells

Mol Endocrinol. 2016 Feb;30(2):248-53. doi: 10.1210/me.2015-1220. Epub 2016 Jan 8.


The 2 most abundant human pancreatic islet cell types are insulin-producing β-cells and glucagon-producing α-cells. Defined cis-regulatory elements from rodent Insulin genes have permitted genetic labeling of human islet β-cells, enabling lineage tracing and generation of human β-cell lines, but analogous elements for genetically labeling human α-cells with high specificity do not yet exist. To identify genetic elements that specifically direct reporter expression to human α-cells, we investigated noncoding sequences adjacent to the human GLUCAGON and ARX genes, which are expressed in islet α-cells. Elements with high evolutionary conservation were cloned into lentiviral vectors to direct fluorescent reporter expression in primary human islets. Based on the specificity of reporter expression for α- and β-cells, we found that rat glucagon promoter was not specific for human α-cells but that addition of human GLUCAGON untranslated region sequences substantially enhanced specificity of labeling in both cultured and transplanted islets to a degree not previously reported, to our knowledge. Specific transgene expression from these cis-regulatory sequences in human α-cells should enable targeted genetic modification and lineage tracing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Genetic Loci
  • Genetic Techniques*
  • HEK293 Cells
  • Humans
  • Insulin-Secreting Cells / metabolism*
  • Islets of Langerhans Transplantation
  • Mice, SCID
  • Regulatory Sequences, Nucleic Acid / genetics
  • Staining and Labeling*