Mass Spectrometry-based Proteome Maps for Human Islet Cells
Contact PI: Klaus Kaetner PhD, MS, Wei-Jun Qian PhD
The islets of Langerhans represent complex endocrine micro-organs that are comprised of multiple cell types. Currently, one major knowledge gap in T1D research involves a lack understanding of the molecular compositions at the proteome level for each human islet cell type. Hence, we envision that the generation of cell type-specific and quantitative proteome maps of the human islet cells will be a significant and timely opportunity for the Human Islet Research Network to establish a foundational resource for the diabetes research community. The objective of this application to the HIRN Opportunity Fund is to establish in-depth cell type-specific proteome maps for human islet cells, including the whole islets, α-cells, and β-cells. This objective is enabled by the advanced mass spectrometry-based proteomics technologies and the new cell isolation technologies for obtaining highly-purified α- and β-cells from human donors. This proposed project will be a collaborative effort between the HIRN consortium on beta-cell death and survival (CBDS) and consortium on targeting and regeneration (CTAR). Highly purified α-cells and β-cells from several human donors will be isolated from several islet preparations from individual organ donors. Comprehensive proteome analyses for whole islets, α-cells, and β-cells will be performed to achieve a depth of coverage of ~10,000 proteins for each cell type. Furthermore, we will leverage recently published whole proteome maps of the intact pancreas and other human tissues to pinpoint islet-cell specific or β-cell specific protein signatures by comparing islet cell proteomes with other available data from human tissues. We anticipate this effort will lead to the first comprehensive proteome maps for human islet cell types as a highly valuable public resource supported by the HIRN. This information will be valuable for defining what are functional human β-cells or islets, for understanding the mechanisms of β-cell death, proliferation, or autoimmune interactions across the HIRN consortia, for identifying β-cell specific protein markers for pre-symptomatic T1D diagnosis, and for generating cell type specific affinity reagents.
Opportunity Pool Project Sponsored by CBDS & CTAR.