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Nature Papers on Long Reads for Bacterial Genomes, Zebrafish Atlas, Hypothalamic Aging in Mammals

A study demonstrating the use of long-read Oxford Nanopore sequencing to generate near-finished bacterial genomes from isolates or metagenomes, without short-read or reference polishing, is presented in Nature Methods this week. Oxford Nanopore sequencing has enabled the recovery of highly contiguous microbial genomes from isolates or metagenome but obtaining near-finished genomes has required the inclusion of short-read polishing to correct insertions and deletions derived from homopolymer regions. In this week's study, a team led by scientists from Aalborg University show that Oxford Nanopore R10.4 enables the generation of near-finished microbial genomes from pure cultures or metagenomes at 40-fold coverage without short-read polishing.

An atlas of zebrafish developmental functional genomic data is presented in Nature Genetics this week, representing a new resource for one of most popular model organisms for studying embryonic development and modeling human diseases. Despite its widespread use, the zebrafish has lacked a systematic functional annotation program akin to those in other animal models. To address this, an international group of investigators formed the DANIO-CODE consortium with the goal of functionally annotating the developing zebrafish genome. As reported this week, the group used published and new data to identify more than 140,000 cis-regulatory elements throughout zebrafish development, including classes with distinct features dependent on their activity in time and space. They delineated the distinct distance topology and chromatin features between regulatory elements active during zygotic genome activation and those active during organogenesis. Further, the team matched regulatory elements and epigenomic landscapes between zebrafish and mouse, and predicted functional relationships between them beyond those gleaned from sequence similarities. 

Using single-nuclei RNA sequencing, a Brown University team has uncovered new details about changes that occur in the mammalian hypothalamus during aging. While changes in metabolism, sleep patterns, body composition, and hormone status are well-established hallmarks of aging, little is known about the effects of aging on the hypothalamus, which controls these behaviors. To investigate, the scientists applied snRNA-seq to 40,064 hypothalamic nuclei from young and aged female mice, revealing cell type-specific signatures of aging in neuronal subtypes as well as astrocytes and microglia. As reported in Nature Aging this week, they also find changes in cell types critical for metabolic regulation and body composition and in an area of the hypothalamus linked to cognition. Notably, the researchers also find a female-specific feature of hypothalamic aging: the elevation of the master regulator of X inactivation, Xist, in hypothalamic neurons. "Understanding how individual populations of cells in this region contribute to overall loss of homeostasis with age will be vital to identifying treatments for aging and age-related disease," the study's authors conclude.