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▎Editor of WuXi AppTec's content team In a paper recently published in the journal Nature, researchers at the University of California San Diego (UCSD) School of Medicine have mapped out the basis of genetic variation that leads to the onset of type 1 diabetes at the cellular level.
Dr.
Joshua Chiou, the first author of the study, said: “This is a key step to find a cure to reverse the course of the disease and ultimately prevent the disease completely.
” This study provides supporting evidence for the role of exocrine pancreas in the pathogenesis of type 1 diabetes, confirming Genetic variation in specific cell types is an important factor in the pathogenesis of type 1 diabetes; at the same time, two methods, genome-wide association studies (GWAS) and single-cell epigenomics, are emphasized, which help to understand the complexity The cellular origin of the disease.
Type 1 diabetes is a chronic autoimmune disease.
The patient's immune system will mistakenly attack its own pancreatic islet β-cells, leading to gradual damage and death of β-cell function.
Eventually, patients need to rely on exogenous insulin for treatment.
For people who are genetically susceptible to type 1 diabetes, the disease has begun to develop before the obvious symptoms of hyperglycemia appear, mainly manifested by the appearance of autoantibodies (anti-insulin and anti-pancreatic antibodies, etc.
) and impaired glucose tolerance.
During this period, the β cells in the pancreas are basically still intact, which provides a crucial window for intervention and preservation of β cells.
Type 1 diabetes is less common than type 2 diabetes, but its prevalence is rising, and there is currently a lack of methods to prevent the onset of type 1 diabetes for high-risk groups.
Image source: 123RF People know very little about the pathogenesis of type 1 diabetes, including how autoimmunity is triggered.
Because this disease is highly heritable, scientists have carried out a number of genome-wide association studies (GWAS) in recent years to find possible genetic code differences.
By comparing the entire genome of patients with the same disease or symptom, this method has determined that most of the genetic variants at risk of type 1 diabetes are located in non-coding regions of the genome.
According to reports, this research team conducted the largest type 1 diabetes GWAS to date, combined with single-cell epigenomics (single-cell epigenomics) analysis methods.
Specifically, they analyzed a total of 520,580 genome samples and identified 69 new associated signals.
Next, an epigenome map of the 448,142 cis-regulatory elements (non-coding DNA sequences within or near genes) in the pancreas and peripheral blood cells was drawn.
This map describes in detail how and when the genes in the cells turn on and Turn off to produce proteins that perform different cellular functions.
▲Some genes regulated by genetic mutations have special pancreatic exocrine function, which affects the risk of type 1 diabetes (picture source: reference [1]) "By combining GWAS with the epigenome map, we can determine the type 1 diabetes-related The function of genetic variation in different types of cells, and the discovery of the predictable causal role of pancreatic exocrine cells in diseases, and then verify it through experiments.
” The corresponding author of the study, Professor Kyle Gaulton, explained.
Among them, the exocrine cells of the pancreas produce enzymes that are secreted into the small intestine to help digest food in the small intestine.
Professor Maike Sander, one of the authors of this study, said that this is a "milestone" study.
These findings represent a major leap for researchers in understanding the cause of type 1 diabetes, meaning that the dysfunction of pancreatic exocrine cells may be type 1.
The main cause of diabetes also provides a roadmap for further determining which exocrine genes may play a role in the pathogenesis.Reference materials: [1] Chiou, J.
, et, al.
(2021).
Interpreting type 1 diabetes risk with genetics and single-cell epigenomics.
Nature.
Published.
https://doi.
org/10.
1038/s41586-021- 03552-w[2] Genetic tools help identify a cellular culprit for type 1 diabetes.
Retrieved May 19, 2021, from https://medicalxpress.
com/news/2021-05-genetic-tools-cellular-culprit-diabetes.
html
Dr.
Joshua Chiou, the first author of the study, said: “This is a key step to find a cure to reverse the course of the disease and ultimately prevent the disease completely.
” This study provides supporting evidence for the role of exocrine pancreas in the pathogenesis of type 1 diabetes, confirming Genetic variation in specific cell types is an important factor in the pathogenesis of type 1 diabetes; at the same time, two methods, genome-wide association studies (GWAS) and single-cell epigenomics, are emphasized, which help to understand the complexity The cellular origin of the disease.
Type 1 diabetes is a chronic autoimmune disease.
The patient's immune system will mistakenly attack its own pancreatic islet β-cells, leading to gradual damage and death of β-cell function.
Eventually, patients need to rely on exogenous insulin for treatment.
For people who are genetically susceptible to type 1 diabetes, the disease has begun to develop before the obvious symptoms of hyperglycemia appear, mainly manifested by the appearance of autoantibodies (anti-insulin and anti-pancreatic antibodies, etc.
) and impaired glucose tolerance.
During this period, the β cells in the pancreas are basically still intact, which provides a crucial window for intervention and preservation of β cells.
Type 1 diabetes is less common than type 2 diabetes, but its prevalence is rising, and there is currently a lack of methods to prevent the onset of type 1 diabetes for high-risk groups.
Image source: 123RF People know very little about the pathogenesis of type 1 diabetes, including how autoimmunity is triggered.
Because this disease is highly heritable, scientists have carried out a number of genome-wide association studies (GWAS) in recent years to find possible genetic code differences.
By comparing the entire genome of patients with the same disease or symptom, this method has determined that most of the genetic variants at risk of type 1 diabetes are located in non-coding regions of the genome.
According to reports, this research team conducted the largest type 1 diabetes GWAS to date, combined with single-cell epigenomics (single-cell epigenomics) analysis methods.
Specifically, they analyzed a total of 520,580 genome samples and identified 69 new associated signals.
Next, an epigenome map of the 448,142 cis-regulatory elements (non-coding DNA sequences within or near genes) in the pancreas and peripheral blood cells was drawn.
This map describes in detail how and when the genes in the cells turn on and Turn off to produce proteins that perform different cellular functions.
▲Some genes regulated by genetic mutations have special pancreatic exocrine function, which affects the risk of type 1 diabetes (picture source: reference [1]) "By combining GWAS with the epigenome map, we can determine the type 1 diabetes-related The function of genetic variation in different types of cells, and the discovery of the predictable causal role of pancreatic exocrine cells in diseases, and then verify it through experiments.
” The corresponding author of the study, Professor Kyle Gaulton, explained.
Among them, the exocrine cells of the pancreas produce enzymes that are secreted into the small intestine to help digest food in the small intestine.
Professor Maike Sander, one of the authors of this study, said that this is a "milestone" study.
These findings represent a major leap for researchers in understanding the cause of type 1 diabetes, meaning that the dysfunction of pancreatic exocrine cells may be type 1.
The main cause of diabetes also provides a roadmap for further determining which exocrine genes may play a role in the pathogenesis.Reference materials: [1] Chiou, J.
, et, al.
(2021).
Interpreting type 1 diabetes risk with genetics and single-cell epigenomics.
Nature.
Published.
https://doi.
org/10.
1038/s41586-021- 03552-w[2] Genetic tools help identify a cellular culprit for type 1 diabetes.
Retrieved May 19, 2021, from https://medicalxpress.
com/news/2021-05-genetic-tools-cellular-culprit-diabetes.
html
