Biology subjects

Yoshinaga, S.

Publications and source records attributed to Yoshinaga, S..

7 recordsLinked to original sources

bioRxiv2026

Photosynthesis-derived carbohydrate supply sustains CuCl2-induced phytoalexin production in rice leaves

Phytoalexins are antimicrobial metabolites whose biosynthesis is triggered by signaling activated by both biotic and abiotic elicitors, but the physiological conditions that sustain their production remain poorly understood. Here, we examined how light and carbohydrate availability affect CuCl2-induced production of diterpenoid (phytocassanes and momilactones) and flavonoid (sakuranetin) phytoalexins in rice (Oryza sativa L.) leaf disks. Darkness strongly suppressed both the accumulation of all three phytoalexin groups and the induction of their biosynthetic genes. In darkness, endogenous sucrose, glucose, and fructose declined to 3%-8% of the levels in the light, whereas early accumulation of jasmonic acid and jasmonoyl-L-isoleucine (JA-Ile) was not detectably reduced. Exogenous sucrose restored phytoalexin accumulation in darkness in a dose-dependent manner, together with the expression of the suppressed biosynthetic genes, whereas equimolar mannitol had no effect. Glucose also restored sakuranetin accumulation in darkness but only partially restored diterpenoid accumulation, whereas the glucose analog 2-deoxy-D-glucose did not, and it suppressed CuCl2-induced accumulation in the light in a dose-dependent manner. In the light, 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), an inhibitor of photosynthetic electron transport, depleted soluble sugars and suppressed phytoalexin accumulation, and sucrose reversed this suppression. Sugars alone induced little phytoalexin accumulation, indicating that carbohydrates act permissively rather than as elicitors. Diterpenoid phytoalexins depended more strongly on light than sakuranetin, yet both classes depended on carbohydrate availability. These results indicate that photosynthesis-derived carbohydrate supply sustains elicitor-induced phytoalexin production in rice leaves and largely accounts for its light dependence.

plant biology↗

bioRxiv2026

Developmental prefrontal myelination shapes inhibitory interneuron function and adult social behavior

Early-life adversity and abnormal myelination are implicated in psychiatric disorders, but how developmental myelination influences adult social cognition remains unclear. Here, we tested whether disrupting developmental myelination in the medial prefrontal cortex (mPFC) impairs adult social behavior. Using complementary genetic strategies in male mice, we suppressed Myelin Regulatory Factor (Myrf)-dependent myelination locally in the juvenile mPFC or broadly in oligodendrocyte-lineage cells. Both approaches selectively impaired adult social novelty preference while sparing sociability, locomotion, and affective behaviors. Focal prefrontal dysmyelination also reduced social dominance. Spatial transcriptomics revealed coupling between myelin-related genes and parvalbumin (PV) interneuron markers in the healthy mPFC, which was disrupted by developmental hypomyelination. Consistent with this transcriptional alteration, PV interneurons showed reduced high-frequency firing despite preserved intrinsic excitability. In the human prefrontal cortex, MBP-PV expression was correlated in controls but not in individuals with schizophrenia. These findings indicate that developmental prefrontal myelination contributes to PV interneuron maturation and suggest that disrupted oligodendrocyte-interneuron coordination may contribute to impaired social recognition.

neuroscience↗

bioRxiv2026

DAP12-deficient microglia adopt a TREM2-independent antigen-presenting state with a glial-to-neuronal cascade in Nasu-Hakola disease

Nasu-Hakola disease (NHD), a dementia with about 200 cases worldwide, is caused by loss-of-function mutation of TYROBP, encoding DAP12, or its receptor TREM2. TREM2-DAP12 is the switch that converts microglia from a surveillant to a reactive state; what DAP12-deficient microglia become and to what extent they reshape their microenvironment is unknown. We profiled prefrontal cortex and hippocampus from an NHD donor and control by single-nucleus RNA sequencing and mapped the glial changes in situ by spatial transcriptomics. NHD microglia adopted a CIITA-driven, MHC class II-high antigen-presenting state with complement, iron and glycolytic programs and Fc receptors but not the TREM2-dependent lipid program. Astrocytes became pan-reactive and lost metallothionein expression, oligodendrocytes lost mature cells and cholesterol synthesis, and excitatory neurons lost presynaptic and activity programs, consistently between regions and across a published cohort. DAP12 deficiency left microglia in an antigen-presenting state short of the TREM2-dependent arm, accompanied by a glial-to-neuronal cascade.

neuroscience↗

bioRxiv2024

Integrative Transcriptomics Reveals Layer 1 Astrocytes Altered in Schizophrenia

Schizophrenia is one of the most prevalent psychiatric disorders with unclear pathophysiology despite a century-long history of intense research. Schizophrenia affects multiple networks across different brain regions. The anterior cingulate cortex (ACC) is the region that connects the limbic system to cognitive areas such as the prefrontal cortex and represents a pivotal region for the etiology of schizophrenia; however, the molecular pathology, considering its cellular and anatomical complexity, is not well understood. Here, we performed an integrative analysis of spatial and single-nucleus transcriptomics of the postmortem ACC of people with schizophrenia, together with a thorough histological analysis. The data revealed major transcriptomics signatures altered in schizophrenia, pointing at the dysregulation of glial cells, primarily in astrocytes. We further discovered a decrease in the cellular density and abundance of processes of interlaminar astrocytes, a subpopulation of astrocytes specific to primates that localize in the layer 1 and influence the superficial cortical microenvironment across layer 1 and layers 2/3 of the cortex. Our study suggests that aberrant changes in interlaminar astrocytes could explain the cell-to-cell circuit alterations found in schizophrenia and represent novel therapeutic targets to ameliorate schizophrenia-associated dysfunction.

neuroscience↗

bioRxiv2023

A single-cell atlas of transcribed cis-regulatory elements in the human genome

Transcribed cis-regulatory elements (tCREs), such as promoters and enhancers, are fundamental to modulate gene expression and define cell identity. The detailed mapping of tCREs at single-cell resolution is essential for understanding the regulatory mechanisms that govern cellular functions. Prior tCRE catalogs, limited by bulk analysis, have often overlooked cellular heterogeneity. We have constructed a tCRE atlas using single-cell 5-RNA-seq, capturing over 340,000 single-cells from 23 human tissues and annotating more than 175,000 tCREs, substantially enhancing the scope and granularity of existing cis-regulatory element annotations in the human genome. This atlas unveils patterns of gene regulation, revealing connections between broadly expressed promoters and cell type-specific distal tCREs. Assessing trait heritability at single-cell resolution with a novel tCRE module-based approach, we uncovered the nuanced trait-gene regulatory relationships across a continuum of cell populations, offering insights beyond traditional gene-level and bulk-sample analyses. Our study bridges the gap between gene regulation and trait heritability, underscoring the potential of single-cell analysis to elucidate the genetic foundations of complex traits. These insights set the stage for future research to investigate the impact of genetic variations on diseases at the individual level, advancing the understanding of cellular and molecular basis of trait heritability.

genomics↗

bioRxiv2020

Comprehensive characterization of migration profiles of murine cerebral cortical neurons during development using FlashTag labeling

In mammalian cerebral neocortex, different regions have different cytoarchitecture, neuronal birthdates and functions. In most regions, neuronal migratory profiles have been speculated similar to each other based on observations using thymidine analogues. Few reports investigated regional migratory differences from mitosis at the ventricular surface. Here, in mice, we applied FlashTag technology, in which dyes are injected intraventricularly, to describe migratory profiles. We revealed a mediolateral regional difference in migratory profiles of neurons that is dependent on the developmental stages, e.g., neurons labeled at E12.5-15.5 reached their destination earlier dorsomedially than dorsolaterally even where there were underlying ventricular surfaces, reflecting sojourning below the subplate. This difference was hardly recapitulated by thymidine analogues, which visualize neurogenic gradient, suggesting biological significance different from neurogenic gradient. These observations advance understanding of cortical development, portraying strength of FlashTag in studying migration, and are thus a resource for studies of normal and abnormal neurodevelopment.

neuroscience↗

bioRxiv2020

Two-photon voltage imaging of spontaneous activity from multiple neurons reveals network activity in brain tissue

Recording the electrical activity of multiple neurons simultaneously would greatly facilitate studies on the structure and function of neuronal circuits. Using fluorescent genetically encoded voltage indicators (GEVI) would be especially desirable, as it would allow cell type-selectivity, longitudinal recordings, and further optical manipulations. By expressing the GEVI ASAP3 via in utero electroporation and rapidly imaging neurons in densely labelled tissues via random-access multi-photon microscopy, we achieve voltage recording of multiple neurons in brain slice with single-trial single-voxel resolution. This approach enables monitoring of subthreshold membrane potential changes and action potentials from multiple locations in soma and dendrites for tens of minutes. By optically recording spontaneous electrical activities in somatosensory cortex neurons, we provide evidence for the development of intralaminar horizontal connections in layer 2/3 with greater sensitivity than calcium imaging. Single-trial optical voltage recordings using ASAP3 thus enables the investigation of network connectivity at cellular resolution.

neuroscience↗