Year: 2016
Type: article
Abstract: 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.
Source: Molecular Endocrinology
DOI: 10.1210/me.2015-1220
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Award: G2684780683
OpenAlex ID: W2225525218