T2D-EOMICS · High throughtput electrophysiological measurements coupled with transcriptomics to reveal cellular dysfunction in type 2 diabetes

High throughtput electrophysiological measurements coupled with transcriptomics to reveal cellular dysfunction in type 2 diabetes

Type 2 diabetes is a long-lasting condition in which the body loses its ability to regulate blood sugar levels. The pancreas is the organ responsible for this function. One of the main reasons for the progression of type 2 diabetes is that the pancreas becomes less capable of producing insulin. This occurs because the cells responsible for making insulin, beta cells, stop working properly. It is not yet fully understood what causes these cells to malfunction. Recent research examining individual cells has shown that not all beta cells are the same—they exhibit different patterns of gene activity. This discovery suggests that it is important to study how these differences relate to the loss of function observed in diabetes. However, a major challenge lies in figuring out how these different types of beta cells actually work and how they communicate with other cells in the pancreas: alpha and delta cells. Cell functionality is largely determined by the genes expressed in each cell, which are eventually translated into proteins. Nowadays, the technique for quantifying how many genes or mRNA a cell has is single-cell RNA transcriptomics. However, transcriptomics alone does not reveal how well a cell performs its tasks. Therefore, the ultimate goal of this project is to couple function and transcriptome in human pancreatic samples. To achieve this, we are developing new methods to simultaneously measure transcriptomes and electrophysiology in islet cells with single-cell resolution. Traditionally, patch-clamp techniques have been used to perform electrophysiological measurements to study pancreatic cell secretion. A researcher can measure about 10 cells per day, and each cell can be measured only once. To scale these measurements, we use high-density microelectrode arrays (HD-MEAs) on small 3 × 3 mm chips. This approach enables the measurement of electrical activity from thousands of cells simultaneously, without damaging them, and facilitates repeated measurements over time, enhancing throughput and reproducibility. This provides us with the framework to understand the individual and collective roles of each cell type in diabetes progression.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз