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Inflammation status modulates the effect of host genetic variation on intestinal gene expression in IBD
Hu S, Uniken Venema W, Westra H et al. Inflammation status modulates the effect of host genetic variation on intestinal gene expression in inflammatory bowel disease. Nat Commun 2021; 121: 1122.
IBD is a complex disease with more than 240 genetic risk loci identified so far. However, little is known about how they contribute to disease development in tissue level. Using snap-frozen biopsies from 112 inflamed and 168 non-inflamed intestinal tissues, Hu et al studied how genetic variants influenced transcription of close-by genes through cis-expression quantitative trait loci (cis-eQTL) using RNA sequencing and genotyping by whole exome sequencing and genome-wide genotyping. A total of 190 inflammation-dependent intestinal cis-eQTLs including known IBD-risk genes and genes encoding immune-cell receptors and antibodies were found. The intestinal cis-eQTLs are inflammation-dependent and certain eQTLs coexpressed with IBD-associated genes, indicating that inflammation-dependent cis-eQTLs are potentially involved in gene–gene interactions. Among the 190 inflammation-dependent intestinal cis-eQTLs, 125 of them showed a significant interaction with cell-type enrichment, illustrating that inflammation-dependent eQTLs might be partially driven by enrichment of specific cell types. Moreover, the inflammation-dependent intestinal cis-eQTLs demonstrated genetic susceptibility under inflammatory conditions. By targeting these inflammation-dependent eQTLs, a new therapy, which is highly specific to both tissues and disease status, can be developed, allowing precision medicine in IBD.
Zoning in on the source of liver regeneration
Wei Y, Wang Y, Jia Y, et al. Liver homeostasis is maintained by midlobular zone two hepatocytes. Science 2021; 371: eabb1625. doi: 10.1126/science.abb1625
The unparalleled regenerative capacity of the liver has long been recognised. However, uncertainty has existed about the cellular origin of regenerating hepatocytes. Specifically, there have been conflicting data as to whether hepatocyte proliferation is stochastically distributed across the liver lobule or if there are specific subpopulations of hepatocytes or stem cells, which repopulate the liver. Recent studies have enabled the detailed dissection of transcriptional differences between hepatocytes …
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.
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