Science Papers Examine Role of Epigenetics in Liver Fibrosis, Present Bdelloid Genome Assembly

Using single-cell omics analysis, a team led by scientists from Sichuan University has identified an epigenetic cause of liver fibrosis, which may lead to a new treatment strategy for nonalcoholic steatohepatitis (NASH) and other chronic hepatic diseases. NASH is a rising cause of chronic disease that leads to fibrosis, cirrhosis, and liver failure. However, the molecular processes underlying the disease’s fibrogenesis are poorly understood. As they report in Science Translational Medicine, the researchers combined single-cell RNA sequencing of human patients and a large-animal NASH model to reveal how epigenetics-dependent maladaptation of sinusoidal-macro vascular hierarchy stimulates a profibrotic T helper 17 cell response in NASH. They also show that targeting the underlying fibrogenic pathway can alleviate fibrosis in a NASH animal model.

The first high-quality chromosome-level genome assembly for the bdelloid Adineta vaga is presented in Science Advances this week. Bdelloid rotifers are notorious as a speciose ancient clade comprising only asexual lineages. Their longevity and diversity also challenge the expectation that obligatory asexual animal lineages, in which recombination and outcrossing are absent, are evolutionary dead ends. A. vaga, in particular, became a model species for its extreme resistance to desiccation, freezing, and ionizing radiation, with implications for space research. To better understand the effects of long-term asexuality and DNA breakage on genome evolution, a group led by investigators from Université de Namur in Belgium constructed the diploid genome assembly, composed of six pairs of homologous chromosomes with a footprint of paleotetraploidy. Among their observations are large-scale losses of heterozygosity, pointing to recombination between homologous chromosomes either during mitotic DNA double-strand break repair or when resolving programmed DNA breaks during a modified meiosis. “Our results trigger the reappraisal of potential meiotic processes in bdelloid rotifers and help unravel the factors underlying their long-term asexual evolutionary success,” the study’s authors write.

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