Table 3.
Emerging technologies for studies of T1D pathology.
| Emerging Technologies/Platforms | Applications | Reference |
|---|---|---|
| Single cell transcriptomics/ proteomics | Assess expression of candidate genes and their protein products for paired cell genotype/phenotype data, as well as adaptive immune cell repertoire analysis | 104 |
| Single cell ATAC‐sequencing | Investigate the contribution of dysregulated gene networks, particularly in candidate loci, to immune or β‐cell function | 106, 107 |
| CyTOF | Following labeling with metal tagged antibodies, deep phenotyping of single cell suspensions can be performed | 110 |
| IMC | By applying metal tagged antibodies to fixed tissue sections, deep phenotyping of cells can be performed in situ | 111, 112 |
| Laser capture microdissection | Identify differentially expressed genes and proteins to develop disease‐predictive biomarkers or targeted therapeutics | 108 |
| nanoPOTS | Identify novel post‐translational modifications within a single islet and the proteomic basis for islet heterogeneity | 109 |
| CODEX | Examine disease‐related tissue and cell subset reorganization, as well as perform multiplexed deep phenotyping | 113 |
| Tissue clearing (e.g. X‐CLARITY, PARS) | Visualization of intact morphology, vasculature, innervation, and extracellular matrix | 114 |
| RNA single‐molecule FISH | Identify the dynamics of candidate gene and checkpoint molecule expression in all subsets present in the tissue microenvironment, examine how they influence cell phenotype and function | 115 |
| Microphysiological Systems | Introduce targeted therapeutics or innate and adaptive immune cells to assess their contribution to disease development/treatment | 116 |
| Investigate the underlying cause of the islet anti‐viral immune signature | ||
| Examine the role of hybrid insulin peptides (HIPs), defective ribosomal products (DRiPs) and neoantigens in β‐cell stress or destruction | ||
| Tissue Slice | Profile live immune and endocrine cells across the pancreas in the native tissue environment | 24 |
| Assess the role of chemokines and adhesion molecules | ||
| Determine which cells are directly pathogenic vs bystander or tissue resident cells |
*
nanoPOTS = Nanodroplet processing in one pot for trace samples; PARS = Perfusion‐assisted agent release in situ; ATAC = Assay for Transposase Accessible Chromatin; CyTOF = Cytometry time of flight; IMC = Imaging mass cytometry.