Biology subjects

Takemoto, K.

Publications and source records attributed to Takemoto, K..

10 recordsLinked to original sources

bioRxiv2026

Graph neural network-based prediction of direct reprogramming factors using gene regulatory networks with microRNA-mediated regulation

Direct reprogramming (DR) converts somatic cells directly into target cell types while bypassing an intermediate pluripotent state, such as induced pluripotent stem cells. In practice, DR is achieved by transfecting multiple transcription factors (TFs); prior research has shown that combining microRNAs (miRNAs) with TFs further improves reprogramming efficiency. However, experimentally identifying effective TFs and miRNA combinations is difficult and costly, underscoring the need for robust in silico prediction approaches. We developed a graph neural network-based method to predict TFs that induce DR across diverse human cell types while explicitly modeling miRNA-mediated transcriptional regulation. By constructing a gene regulatory network integrating TF-target gene, TF-miRNA, miRNA-target gene, and gene-gene interactions, we implemented a Graph Attention Network v2 that predicts DR-inducing TFs while learning interaction importance and capturing transcriptional activation and repression. This approach outperformed existing methods in predicting experimentally validated DR-inducing TFs. Moreover, high-ranking predictions for previously unexplored tissues included TFs known to be associated with the development of the corresponding tissues, supporting the biological relevance of the results. Overall, the proposed method provides a practical in regenerative medicine.

bioinformatics↗

bioRxiv2026

DeepSpaceDB 2.0: an interactive spatial transcriptomics database for large-scale Xenium data exploration

The 10x Genomics Xenium platform enables high-resolution spatial transcriptomics at single-cell and subcellular scales, but effective reuse of public Xenium datasets is hindered by large data sizes and heterogeneous file formats. We previously developed DeepSpaceDB, a spatial transcriptomics database designed for interactive, in-depth analysis of tissues and tissue microenvironments. Here, we present a major expansion of DeepSpaceDB that integrates large-scale single-cell spatial transcriptomics data generated by the Xenium platform. In this update, we systematically collected 1,539 public Xenium datasets from multiple repositories and processed them through a robust, standardized pipeline that validates, repairs, and harmonizes heterogeneous inputs into a unified representation. To support efficient exploration of these data, we introduced a redesigned DeepSpaceDB interface and complementary Zarr-based storage formats optimized for gene-centric visualization and spatially localized queries, enabling sub-second response times for common interactive operations. The updated platform supports real-time visualization of spatial data and analysis of regions of interest directly in the web browser. Together, this expansion establishes DeepSpaceDB as a unified resource for single-cell spatial transcriptomics, substantially lowering the barrier to accessing, exploring, and reusing large-scale public Xenium datasets.

bioinformatics↗

bioRxiv2025

Opponent-flipping tactics in aggressive interactions of the cricket Gryllus bimaculatus

Male crickets engage in intense aggressive behavior, competing for resources. In this study, we focus on the quick movements during tactile combat in the cricket fight, to understand how they defeat the opponents. We performed kinematic analysis following high-speed cam recording of the fight. High-speed cam recordings showed that the attacker jumped to the head of the attacked cricket and thrusted it backwards. The attacked cricket was sometimes flipped over and tended to retreat. To understand how the attacker jumps effectively to flip over the opponent, we compared the attack-jump and escape-jump. The kinematics analysis demonstrated that the attack motion is different from the jump in the case of escaping from threats. The attacker cricket adjusted the direction of its body using its forelegs. The mandibles were used to hook onto the head of the attacked cricket. The attacked cricket moved its hindlegs with different kinematics to jump in the case of escape and exerted greater velocity. These findings advance our knowledge of how animals utilize their body depending on the situation.

animal behavior and cognition↗

bioRxiv2025

DeepSpaceDB: a spatial transcriptomics atlas for interactive in-depth analysis of tissues and tissue microenvironments

Spatial transcriptomics provides a revolutionary approach to mapping gene expression within tissues, offering critical insights into the spatial organization of cellular and molecular processes. However, generating new spatial transcriptomics data is expensive and technically demanding, and analyzing such data requires advanced bioinformatics expertise. While publicly available datasets are growing rapidly, existing databases offer limited tools for interactive exploration and cross-sample comparisons. Here, we introduce DeepSpaceDB, a next-generation spatial transcriptomics database designed to address these issues. DeepSpaceDB focuses on interactivity and advanced analytical functionality, enabling users to explore spatial transcriptomics data with unprecedented flexibility. DeepSpaceDB allows for interactive selection and comparison of gene expression across regions within a single tissue slice or between slices, such as comparing hippocampal regions of an Alzheimers model mouse and a control. It also includes quality indicators, database-wide trends, and advanced visualizations that provide real-time interactivity, such as zoomable plots and hover-based information display. Moreover, these functions are not restricted to the samples collected in our database but can also be applied to samples uploaded by users. The current version of DeepSpaceDB focuses explicitly on samples of the 10X Genomics Visium platform, ensuring higher-quality analyses and enhanced exploration tools, including comparison between interactively selected regions of tissue sections. This tradeoff enables unique features like similarity-based sample embeddings and database-wide comparisons, setting it apart from other databases prioritizing broad platform coverage over functionality. With its combination of advanced tools and interactive capabilities, DeepSpaceDB represents a transformative resource for spatial transcriptomics research, paving the way for deeper insights into tissue organization and disease biology. Availability: DeepSpaceDB is available at www.deepspacedb.com.

bioinformatics↗

bioRxiv2021

FBXO47 is essential for preventing the synaptonemal complex from premature disassembly in mouse male meiosis

Meiotic prophase is a prolonged G2 phase that ensures the completion of numerous meiosis-specific chromosome events. During meiotic prophase, homologous chromosomes undergo synapsis to facilitate meiotic recombination yielding crossovers. It remains largely elusive how homolog synapsis is temporally maintained and destabilized during meiotic prophase. Here we show that FBXO47 is the stabilizer of synaptonemal complex during male meiotic prophase. Disruption of FBXO47 shows severe impact on homologous chromosome synapsis and DSB repair processes, leading to male infertility. Notably, in the absence of FBXO47, although once homologous chromosomes are synapsed, the synaptonemal complex is precociously disassembled before progressing beyond pachytene. Remarkably, Fbxo47 KO spermatocytes remain in earlier stage of meiotic prophase and lack crossovers, despite apparently exhibiting diplotene-like chromosome morphology. We propose that FBXO47 functions independently of SCF E3 ligase, and plays a crucial role in preventing synaptonemal complex from premature disassembly during cell cycle progression of meiotic prophase.

cell biology↗

bioRxiv2021

The polyol pathway is an evolutionarily conserved system for sensing glucose uptake

Cells must adjust the expression levels of metabolic enzymes in response to fluctuating nutrient supply. For glucose, such metabolic remodeling is highly dependent on a master transcription factor ChREBP/MondoA. However, it remains elusive how glucose fluctuations are sensed by ChREBP/MondoA despite the stability of major glycolytic pathways. Here we show that in both flies and mice, ChREBP/MondoA activation in response to glucose ingestion depends on an evolutionarily conserved glucose-metabolizing pathway: the polyol pathway. The polyol pathway converts glucose to fructose via sorbitol. It has been believed that this pathway is almost silent, and its activation in hyperglycemic conditions has deleterious effects on human health. We show that the polyol pathway is required for the glucose-induced nuclear translocation of Mondo, a Drosophila homologue of ChREBP/MondoA, which directs gene expression for organismal growth and metabolism. Likewise, inhibition of the polyol pathway in mice impairs ChREBPs nuclear localization and reduces glucose tolerance. We propose that the polyol pathway is an evolutionarily conserved sensing system for the glucose uptake that allows metabolic remodeling.

physiology↗

bioRxiv2021

Meiosis-specific ZFP541 repressor complex promotes meiotic prophase exit during spermatogenesis

During spermatogenesis, meiosis is accompanied by robust alteration in gene expression and chromatin status. However, it remained elusive how meiotic transcriptional program is established to ensure completion of meiotic prophase. Here, we identified a novel protein complex consisting of germ-cell-specific zinc-finger protein ZFP541 and its interactor KCTD19 as the key transcriptional regulator for meiotic prophase exit. Our genetic study showed that ZFP541 and KCTD19 are co-expressed from pachytene onward and play an essential role in the completion of meiotic prophase program in the testis. Furthermore, our ChIP-seq and transcriptome analyses revealed that ZFP541 binds to and suppresses a broad range of genes whose function is associated with biological processes of transcriptional regulation and covalent chromatin modification. The present study demonstrated that germ-cell specific ZFP541-KCTD19 containing complex promotes meiotic prophase exit in males, and triggers reconstruction of the transcription network and chromatin organization leading to post-meiotic development.

developmental biology↗

bioRxiv2020

Diversity of dominant soil bacteria increases with warming velocity at the global scale

Understanding global soil bacterial diversity is important because of the key roles soil bacteria play in the global ecosystem. Given the effects of environmental changes (e.g., climate change and human effect) on the diversity of animals and plants, effects on soil bacterial diversity are expected; however, they have been poorly evaluated to date. Thus, in this study, we focused on the soil dominant bacteria because of their global importance and investigated the effects of warming velocity and human activities on their diversity. Using a global dataset of bacteria, we performed spatial analysis to evaluate the effects, while statistically controlling for the potential confounding effects of current climate and geographic parameters with global climate and geographic data. It was demonstrated that the diversity of the dominant soil bacteria was influenced globally by warming velocity (showing significant increases) in addition to aridity index (dryness) and pH. The effects of warming velocity were particularly significant in forests and grasslands. An effect from human activity was also observed, but it was secondary to warming velocity. These findings provide robust evidence, and advance our understanding of the effects of environmental changes (particularly global warming) on soil bacterial diversity at the global scale.

ecology↗

bioRxiv2020

Phosphorylation of the Anaphase Promoting Complex activator CDH1/FZR regulates the transition from Meiosis I to Meiosis II in mouse male germ cell

CDH1/FZR is an activator of Anaphase promoting complex/Cyclosome (APC/C), best known for its role as E3 ubiquitin ligase that drives the cell cycle. APC/C activity is regulated by CDK-mediated phosphorylation of CDH1 during mitotic cell cycle. Although the critical role of CDH1 phosphorylation has been shown mainly in yeast and in vitro cell culture studies, its biological significance in mammalian tissues in vivo remained elusive. Here, we examined the in vivo role of CDH1 phosphorylation using a mouse model, in which non-phosphorylatable substitutions were introduced in the putative CDK-phosphorylation sites of CDH1. Although ablation of CDH1 phosphorylation did not show substantial consequences in mouse somatic tissues, it led to severe testicular defects resulting in male infertility. In the absence of CDH1 phosphorylation, male juvenile germ cells entered meiosis normally but skipped meiosis II producing diploid spermatid-like cells. In aged testis, male germ cells were overall abolished, showing Sertoli cell-only phenotype. The present study demonstrated that phosphorylation of CDH1 is required for temporal regulation of APC/C activity at the transition from meiosis I to meiosis II, and for spermatoginial stem cell maintenance, which raised an insight into the sexual dimorphism of CDH1-regulation in germ cells.

cell biology↗

bioRxiv2020

A meiosis-specific factor MRM/C19orf57 modulates localization of RAD51 and DMC1 recombinases to DSBs in mouse meiotic recombination

Meiotic recombination is critical for genetic exchange and generation of chiasmata that ensures faithful chromosome segregation during meiosis I. Meiotic recombination is initiated by DNA double-strand break (DSB) followed by multiple processes of DNA repair. The exact mechanisms how recombinases localize to DSB remained elusive. Here we show that C19orf57/4930432K21Rik/BRME1 is a new player for meiotic recombination in mice. C19orf57/4930432K21Rik/BRME1 associates with ssDNA binding proteins, BRCA2 and MEILB2/HSF2BP, critical recruiters of recombinases onto DSB sites. Disruption of C19orf57/4930432K21Rik/BRME1 shows severe impact on DSB repair and male fertility. Remarkably, removal of single stranded DNA (ssDNA) binding proteins from DSB sites is delayed, and reciprocally the loading of RAD51 and DMC1 onto resected ssDNA is impaired in Brme1 KO spermatocytes. We propose that C19orf57/4930432K21Rik/BRME1 modulates localization of recombinases to meiotic DSB sites through the interaction with the BRCA2-MEILB2/HSF2BP complex during meiotic recombination.

molecular biology↗