Biology subjects

Omori, K.

Publications and source records attributed to Omori, K..

7 recordsLinked to original sources

bioRxiv2026

Circadian feeding rhythm loss drives sex-specific β-cell dysfunction in diet-induced obesity

Diet-induced obesity (DIO), modeled by a high-fat diet (HFD), adversely affects circadian glucose homeostasis partly by dysregulating fasting/feeding cycles. However, its impact on circadian {beta}-cell function and relevant transcriptional programs remains unclear. To investigate this, we exposed male and female C57BL/6 mice to either chow or HFD for eight weeks and assessed behavioral (feeding/activity), physiological (glucose tolerance/insulin secretion), transcriptomic (RNA sequencing (RNA-seq)), and epigenomic (Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-seq)) circadian rhythms. Additionally, we tested whether normalizing fasting/feeding cycles via time-restricted feeding (tRF) during the dark- or light-phase of the circadian cycle could mitigate DIO's deleterious effects. DIO disrupted circadian fasting/feeding rhythms, with greater disruption in males than females (p<0.05 vs. CHOW). In males, DIO abolished circadian regulation of glucose tolerance and in vivo glucose-stimulated insulin secretion (GSIS) (p<0.05 vs. chow), whereas female mice maintained circadian glucose homeostasis. RNA-seq analysis of male islets revealed a 42.1% reduction in circadian-regulated transcripts under DIO, with weakened rhythms in key {beta}-cell pathways such as insulin secretion. Moreover, ATAC-Seq analysis indicated reduced chromatin accessibility of genes/pathways related to insulin secretion and glucose hemostasis under DIO (p<0.05 vs. chow) during both dark- or light-phase of the circadian cycle. Notably, dark-phase time-restricted feeding (tRF) restored circadian glucose tolerance, GSIS, and islet gene expression, whereas light-phase tRF enhanced {beta}-cell function during the normally inactive/light phase of the circadian cycle, further suppressing circadian rhythmicity of the islet transcriptome. Motif analysis indicated that DIO suppressed the activity of D-box transcription factors (TFs) (DBP and TEF) while enhancing the activity of ETS family TFs (ELK1, ETS2, ELF2, and GABPA), which was partly mitigated by dark-phase tRF. Our study demonstrates that DIO disrupts circadian {beta}-cell function and gene expression by dysregulating fasting/feeding cycles in male mice and reveals significant sex differences in how DIO affects circadian glucose homeostasis and {beta}-cell function.

physiology↗

bioRxiv2026

Adolescent prodromal phenotypes of psychiatric disorders: insights from a novel DISC1-perturbed monkey model

Neurodevelopmental deficits frequently lead to mild but significant adolescent social and cognitive changes, representing prodromal manifestations of adult-onset psychiatric disorders in a cross-disease manner. Although experimental medicine utilizes animal models to address the mechanisms, rodent brains lack critical structures for human higher brain functions such as the dorsolateral prefrontal cortex. To fill this translational gap, we generated monkeys with an impaired DISC1 gene locus, targeting the multifunctional protein essential for neurodevelopment and involved in transdiagnostic mental health risks. Here we analyze the F0 animals by minimizing mosaicism. At ages equivalent to human adolescence, these monkeys exhibited blunted responsiveness to social stimuli and increased internal drives, mirroring altered social behaviors in the prodromal stage in humans. Resting-state functional MRI data indicated disrupted global functional connectivity and reorganization of network topology, marked by a shift in the dominance of brain hubs from prefrontal regions to sensory areas. This primate model provides a unique platform for studying psychiatric disorders, such as schizophrenia, across the developmental trajectory.

neuroscience↗

bioRxiv2025

Identification of stem cell marker-positive subpopulations in the vocal fold of the larynx through transcriptomic analyses

Information on the maintenance of tissue homeostasis is important for the development of effective therapeutic methods, however, reports on the cellular composition and tissue stem cells of the larynx were scarce. Therefore, we analyzed mouse laryngeal mucosa using scRNA-seq, and spatial transcriptomics by photo-isolation chemistry, and performed the generation of laryngeal organoid used as an in vitro model from mouse laryngeal mucosa. As a result, we found a SOX9-positive basal cell subpopulation and a Lgr5-positive fibroblast subpopulation in the mouse vocal fold, and obtained three types of epithelial organoids from laryngeal epithelium. We also confirmed the differences in pseudostratified ciliated columnar epithelium composition between the supraglottis and subglottis of the mouse larynx. These findings provide novel insights and valuable tools for future research in laryngology and stem cell biology.

cell biology↗

bioRxiv2023

EBF1 limits the numbers of cochlear hair and supporting cells and forms the scala tympani and spiral limbus during the development of the inner ear

Early B-cell factor 1 (EBF1) is a basic helix-loop-helix transcription factor essential for the differentiation of various tissues. Our single-cell RNA sequencing data suggest that Ebf1 is expressed in the sensory epithelium of the inner ear. Here, we found that the Ebf1 gene and its protein are expressed in the prosensory domain of the inner ear, medial region of the cochlear floor, inner ear mesenchyme, and cochleo-vestibular ganglion. Ebf1 deletion results in incomplete formation of the spiral limbus and scala tympani, increased number of cells in the organ of Corti and Kollikers organ, and aberrant course of the spiral ganglion axons. The inner ear-specific deletion of Ebf1 revealed that scala tympani formation depended on Ebf1 expressed in the otic mesenchyme. Ebf1 deletion in the cochlear epithelia caused the proliferation of SOX2-positive cochlear cells at E13.5, indicating that EBF1 suppresses the proliferation of the prosensory domain and cells of Kollikers organ to facilitate the development of appropriate numbers of hair and supporting cells. Furthermore, mice with deletion of cochlear epithelium-specific Ebf1 showed poor postnatal hearing function. Our results suggest that Ebf1 is essential for normal auditory function in mammals.

developmental biology↗

bioRxiv2022

Single-cell RNA-seq reveals stepwise fate conversion of supporting cells to hair cells in the chick auditory epithelium

In contrast to mammals, the avian cochlea, specifically the basilar papilla, can regenerate sensory hair cells, which involves fate conversion of supporting cells to hair cells. To determine the mechanisms for converting supporting cells to hair cells, we used single-cell RNA sequencing during hair cell regeneration in explant cultures of chick basilar papillae. We identified dynamic changes in the gene expression of supporting cells, and the pseudotime trajectory analysis demonstrated the stepwise fate conversion from supporting cells to hair cells. Initially, supporting cell identity was erased and transition to the precursor state occurred. A subsequent gain in hair cell identity progressed together with downregulation of precursor-state genes. Transforming growth factor beta receptor 1-mediated signaling was involved in induction of the initial step, and its inhibition resulted in suppression of hair cell regeneration. Our data provide new insights for understanding fate conversion from supporting cells to hair cells in avian basilar papillae.

neuroscience↗

bioRxiv2021

The oncogenic Runx3-Myc axis defines p53-deficient osteosarcomagenesis

Osteosarcoma (OS) in human patients is characterized by genetic alteration of TP53. Osteoprogenitor-specific p53-deleted mice (OS mice) have been widely used to study the process of osteosarcomagenesis. However, the molecular mechanisms responsible for the development of OS upon p53 inactivation remain largely unknown. In this study, we detected prominent RUNX3/Runx3 expression in human and mouse p53-deficient OS. Myc was aberrantly upregulated by Runx3 via mR1, a consensus Runx site in the Myc promoter, in a manner dependent on p53 deficiency. Reduction of the Myc level by disruption of mR1 or Runx3 knockdown decreased the tumorigenicity of p53-deficient OS cells and effectively suppressed OS development in OS mice. Furthermore, Runx inhibitors exerted therapeutic effects on OS mice. Together, these results show that p53 deficiency promotes osteosarcomagenesis in human and mouse by allowing Runx3 to induce oncogenic Myc expression.

cancer biology↗

bioRxiv2018

Microbiome composition comparison in oral and atherosclerotic plaque from patients with and without periodontitis

There is no conclusive evidence regarding a causal relationship between periodontitis and atherosclerosis. In this study, we examined the microbiome in the oral cavity and atheromatous plaques from atherosclerosis patients with or without periodontitis to investigate the role of oral bacteria in the formation of atheromatous plaques. We chose four patients with and without periodontitis, who had undergone carotid endarterectomy. Bacterial samples were extracted from saliva on the tongue surface, from periodontal pocket (during the oral examination), and from the atheromatous plaques. We investigated the general and oral conditions from each patient and performed next-generation sequencing analysis for all bacterial samples. There were no significant differences between both groups concerning general conditions. However, the microbiome patterns of the gingival pocket showed differences depending on the absence or presence of periodontitis, while those of the saliva were relatively similar. The microbiome pattern of the atheromatous plaques was entirely different from that in saliva present on the tongue surface and gingival pocket, and oral bacteria were seldom detected. However, the microbiome pattern in atheromatous plaques was different in the presence or absence of periodontitis. These results indicated that oral bacteria did not affect the formation of atheromatous plaques directly. However, the metabolic products of microbiome or the host inflammatory response might indirectly influence the composition of atheromatous plaques.

microbiology↗