Good news!
"Researchers ... have constructed a high-resolution cellular map of Crohn’s disease, a chronic condition in which a hyperactive immune system causes inflammation throughout the gut, leading to symptoms including abdominal pain, diarrhea, and weight loss. ...
The atlas is the largest study of single cells from Crohn’s patients to date, and contains the gene expression profiles of more than 700,000 cells from 71 healthy individuals and patients in varying states of inflammation. ...
the findings offer a detailed cellular portrait into the biological processes underlying Crohn’s that are unique to the small and large intestines. The data also reveal genes and pathways involved in complications of the disease, which could one day be targeted by new drugs. Moreover, the results could help researchers predict and ultimately prevent flares of symptoms, or understand why some patients respond to treatments and others don’t. ...
“We’re beginning to see that Crohn’s disease is not one disease, and that it has many subtypes,” ...
“We’re beginning to see that Crohn’s disease is not one disease, and that it has many subtypes,” ...
They studied inflamed and non-inflamed cells from both segments of the gastrointestinal tract: the large intestine and the ileum, the last segment of the small intestine that is often affected in Crohn's disease.
The scientists used single-cell RNA sequencing to analyze gene activity in the individual gut cells. They found that immune cells and the stroma — the cells inside the gut that shape and support underlying connective tissue — changed in composition during disease. The lining of the intestines showed more changes in gene expression, with some changes unique to the large or small intestine. They also found that expression of genes previously linked to disease risk was distinct in each organ. ...
[only] About 50 to 60 percent of Crohn’s patients respond to drugs and some experience a relapse of symptoms. ... this suggests that Crohn’s is caused by a variety of biological mechanisms requiring treatments that are tailored to individual patients. ... that many of their team’s findings point towards possible targets for personalized treatments. For instance, they identified three genes involved in collagen production that likely contribute to scar tissue in the gut, making the intestines stiffer and less able to pass along food — a common complication of Crohn’s.
To their surprise, the researchers discovered that Crohn’s patients had certain gene expression signatures even when their tissues didn’t look inflamed. ..."
From the highlights and abstract:
"Highlights
• scRNA-seq atlas of 720,633 ileal and colonic cells in Crohn’s disease (CD) and controls
• Compositional and transcriptomic changes across immune, epithelial, and stromal cells
• Colonic tissues show stronger transcriptomic changes in inflammation and disease
• CHMP1A, TBX3, and RNF168 may regulate a CD-associated program in fibroblasts
Summary
Crohn’s disease (CD) is a chronic gastrointestinal disease that is increasing in prevalence worldwide. CD is multifactorial, involving the complex interplay of genetic, immune, and environmental factors, necessitating a system-level understanding of its etiology. To characterize cell-type-specific transcriptional heterogeneity in active CD, we profiled 720,633 cells from the terminal ileum and colon of 71 donors with varying inflammation status. Our integrated datasets revealed organ- and compartment-specific responses to acute and chronic inflammation; most immune changes were in cell composition, whereas transcriptional changes dominated among epithelial and stromal cells. These changes correlated with endoscopic inflammation, but small and large intestines exhibited distinct responses, which were particularly apparent when focusing on IBD risk genes. Finally, we mapped markers of disease-associated myofibroblast activation and identified CHMP1A, TBX3, and RNF168 as regulators of fibrotic complications. Altogether, our results provide a roadmap for understanding cell-type- and organ-specific differences in CD and potential directions for therapeutic development."
The landscape of immune dysregulation in Crohn’s disease revealed through single-cell transcriptomic profiling in the ileum and colon (no public access)
Graphical abstract
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