Researchers have introduced a new method for the precise assessment of cell composition in the human pancreas based on DNA methylation, addressing a critical gap in diabetes research. By overcoming the limitations of traditional protein marker-based approaches, the study offers a more precise means of identifying specific cell types. The results provide insights into beta cell dysfunction in different types of diabetes and have direct clinical implications by improving our understanding of diabetes development and possibly leading to personalized treatment strategies. This innovative molecular alternative to immune detection methods holds promise for broader applications in molecular biology and diagnostics.
In a study published in Diabetes, Prof. Yuval Dor and his research team at the Hebrew University presented a new approach for the accurate assessment of cell composition in the human pancreas and islets. The research addresses a crucial need in understanding the onset of diabetes and provides an alternative to conventional protein marker-based methods.
Current methods rely on the detection of protein markers such as insulin to identify specific cell types in the pancreas. However, the variability of protein content under various physiological and pathological conditions poses a significant limitation and complicates the accurate determination of cell numbers.
The study demonstrates the innovative use of cell type-specific DNA methylation markers to overcome these limitations. By identifying genomic loci that are uniquely demethylated in specific pancreatic cell types, the research team applied targeted PCR to assess the methylation status of these loci in human islet and pancreas samples. This allowed for a precise inference of cell type composition and provided a molecular alternative to conventional immune detection methods.
The researchers examined groups of cells in the pancreas called islets. They found that in individuals with different types of diabetes (pre-T1D, T1D, and T2D), the function of a specific cell type called beta cells was similar but lower compared to individuals without diabetes. When they examined pancreatic tissue from individuals with recently diagnosed type 1 diabetes, they found that beta cell function was within the normal range, indicating an issue with these cells. In individuals with type 2 diabetes, there were more cells of another cell type called alpha cells, but the function of beta cells was normal. This helps us understand how these cells function in diabetes.
The use of DNA methylation-based analysis not only allows for a more precise assessment of cell types in the human pancreas but also proves to be invaluable in interpreting insulin secretion tests. „This method opens up new avenues for understanding pancreatic cell composition in both health and disease.“
Prof. Yuval Dor, lead researcher
The study was led by doctoral student Zeina Drawshy, Dr. Agnes Klochendler, and Prof. Yuval Dor from the Hebrew University in collaboration with scientists from the Hadassah Medical Center, the University of Florida, the University of Pennsylvania, and the Li Ka Shing Center for Research in Edmonton.
Hebrew University of Jerusalem
Drawshy, Z., et al. (2024). DNA methylation-based assessment of cell composition in the human pancreas and its islets. Diabetes. doi.org/10.2337/db23-0704.