Biology subjects

Ishitani, T.

Publications and source records attributed to Ishitani, T..

4 recordsLinked to original sources

bioRxiv2026

Near-complete genome assembly of the African turquoise killifish enables locus-level profiling of transposable element expression

Tandem repeats (TRs) and transposable elements (TEs) occupy substantial fractions of eukaryotic genomes, yet how repeat detection programs affect downstream expression analyses remains poorly explored. Here, we present an improved chromosome-scale assembly of the African turquoise killifish, Nothobranchius furzeri. The assembly matches experimentally estimated genome size and chromosome number. It resolves highly expanded TRs that occupy up to 28.0% of the whole genome. Using this assembly and other complete vertebrate genome assemblies, we compared TR and TE-derived regions across combinations of TR detection programs and TE consensus library construction workflows under a standardized TE classification scheme. Choices in TR detection reshaped the apparent TE landscape. TE workflows shared a broad core of TE-derived regions but recovered complementary sets of age- and sex-associated TE loci, evaluated with a sex-balanced killifish multi-tissue aging cohort. Together, the combinatorial use of adaptable programs supports robust, locus-aware detection of complex repeats across genome assemblies.

genomics↗

bioRxiv2026

Inhibition of the gut ceramidase Asah2 decelerates the vertebrate ageing rate

The pace of ageing varies markedly among vertebrate species and individuals. However, the mechanisms underlying these differences in ageing rates remain unclear. Here, we show that the activity of the gut ceramidase Asah2 determines species- and strain-specific rates of vertebrate ageing. Comparative genomic analyses of vertebrate species and strains with different ageing rates reveal an association between low Asah2 activity and increased lifespan. Using the ultra-short-lived killifish Nothobranchius furzeri as a model, we demonstrate that knockout of Asah2 (asah2 KO) extends lifespan and attenuates systemic ageing phenotypes, including declines in locomotor activity, abnormal protein accumulation in the brain, and accumulation of senescent cells in the liver. asah2 KO elevates levels of ceramide species with long-chain fatty acids in the intestine, and supplementation with these ceramide species suppresses ageing phenotypes and extends lifespan in wild-type fish. asah2 KO and ceramide supplementation alter gut microbiota composition, and asah2 KO-derived microbiota transplantation attenuates ageing phenotypes, suggesting that reduced Asah2 activity prevents ageing through intestinal ceramide-mediated modulation of the microbiota. Given the evolutionary conservation of the Asah2 gene and its age-dependent upregulation in fish and humans, Asah2 and ceramides may act as ageing accelerators and decelerators, respectively, across animal species.

developmental biology↗

bioRxiv2026

Endogenous cell competition kills pathogenic de novo mutant cells but declines under pH stress

Although endogenous cell competition safeguards embryonic development by eliminating unfit cells, the intrinsic origins of unfitness remain unclear. Here, zebrafish whole-genome sequencing and imaging reveal that endogenous cell competition removes cells with spontaneous de novo mutations in key developmental signalling pathways and in human disease-associated genes, such as those associated with Alzheimers disease, epilepsy, autism, and premature aging. These mutations arise frequently during normal development but are efficiently eliminated under physiological conditions, thereby preventing the clonal expansion of harmful cells. However, environmental pH stress disrupts this surveillance by dysregulating Ca2+ signals, allowing mutant cells to persist and resulting in tissue mispatterning and morphological defects. Our findings establish endogenous cell competition as an intercellular communication-dependent genome quality-control mechanism that removes pathogenic mutant cells before clonal expansion. This link between developmental robustness, environmental stress, and mosaic genetic disorders highlights how intrinsic mutations and extrinsic stressors together shape disease susceptibility across the lifespan.

cell biology↗

bioRxiv2018

Cell competition corrects noisy Wnt morphogen gradients to achieve robust patterning

Morphogen signaling forms an activity gradient and instructs cell identities in a signaling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signaling and consequent noisy morphogen gradient. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/{beta}-catenin signaling-gradient, which acts as a morphogen to establish embryonic anterior-posterior patterning, revealed that unfit cells with abnormal Wnt/{beta}-catenin activity spontaneously appear and produce noise in the Wnt/{beta}-catenin-gradient. Communication between the unfit and neighboring fit cells via cadherin proteins stimulates the apoptosis of the unfit cells by activating Smad signaling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/{beta}-catenin-gradient formation and consequent anterior-posterior patterning. Because this gradient controls patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.

cell biology↗