Biology subjects

Matsuda, H.

Publications and source records attributed to Matsuda, H..

13 recordsLinked to original sources

bioRxiv2026

Two closely related RNA helicases, UAP56 and URH49, couple mRNA splicing and export pathways with their distinct complexes

Transcription and mRNA processing are integrated into appropriate mRNA export pathway(s) enabling fine-tuned gene expression. The closely related RNA helicases, UAP56 and URH49, form distinct complexes known as the apo-TREX and the apo-AREX complexes, respectively, which remodel into the ATP-TREX complexes, thus forming multiple mRNA export pathways. However, the mechanisms by which helicases and their complexes shape these pathways remain unclear. Here, we showed that UAP56 and URH49 play general roles in mRNA splicing ahead of export. Further analyses revealed three patterns of splicing regulation and their association with mRNA export: Type I, in which both helicases redundantly or synergistically regulate splicing within the same transcripts, associated with cooperative mRNA export; Type II, in which either helicase preferentially regulates splicing in distinct transcripts; and Type III, in which the helicases exert opposing splicing effects within the same transcripts. Type II and III regulation was associated with selective mRNA export. Moreover, we demonstrated that the distinct complex formation influenced the splicing patterns regulated by the two helicases. Our findings reveal an additional layer of transcriptome regulation mediated by UAP56, URH49, and their complexes, extending beyond their canonical roles in mRNA export.

molecular biology↗

bioRxiv2026

Minimally invasive measurement of maternal transcripts enables predicting the developmental potential of mammalian zygotes

Maternal transcripts are stored in the oocyte cytoplasm during oogenesis and play a pivotal role in early embryonic development after fertilization. However, specific maternal transcripts that reflect the developmental potential of embryos have not been systematically identified, and the use of maternal transcript levels as an indicator of successful development has not been explored. Here, we link the maternal transcriptome to the zygotes developmental potential by examining transcripts in a single polar body. The transcriptome of a zygote or an oocyte was highly similar to that of its accompanying polar body in mouse, cow, and human. We have identified a set of maternal transcripts whose expression levels fluctuate between poor- and good-quality zygotes. Specifically, Sipa1and Zmym6 were identified as marker transcripts that accurately reflect the developmental potential of zygotes. Using these marker genes, combined with machine learning, the development of zygotes to the blastocyst stage was successfully predicted with more than 80% specificity as early as 12 hours after fertilization. Furthermore, our prediction platform significantly improved implantation rates and live births to term. Thus, we have demonstrated a minimally invasive method for identifying maternal transcripts associated with zygote developmental potential. Our developed prediction system provides a generalizable conceptual framework for human infertility treatment to reduce the risk of implantation failure by excluding embryos with low developmental potential, especially when early embryos are transferred, and for livestock propagation to assess selected expressed maternal trait-associated variants before embryo transfer.

developmental biology↗

bioRxiv2026

Enabling Stable Cortical Reconstruction in the HCP Pipeline at Standard Resolution Using FastSurfer Integration with Hybrid T2w- and T1w-based Masking

This study aimed to enable stable cortical reconstruction within the Human Connectome Project (HCP) pipeline under standard-resolution (1 mm3) conditions by developing an integrated framework combining FastSurfer with a hybrid T2w- and T1w-based masking strategy. We implemented a FastSurfer-integrated HCP pipeline incorporating a hybrid masking approach (t2log-hybrid) to stabilize cortical reconstruction, where SynthStrip-derived masks were refined using log-transformed T2-weighted and squared T1-weighted images. An anterior commissure-anchored spatial switching mechanism selectively replaced artifact-prone T2w regions with T1w-derived information in orbitofrontal areas. Performance was evaluated against FreeSurfer v6 (FS6), v7 (FS7), and FastSurfer using geometric agreement, regional consistency, and vertex-wise thickness-myelin analyses. The proposed framework reduced total processing time by over 50% compared with FS6 and maintained high geometric agreement with modern pipelines (vertex-wise r = 0.970 vs FastSurfer; r = 0.929 vs FS7). Agreement with FS6 was lower (r = 0.842), reflecting systematic differences in boundary definition rather than random error. The hybrid masking approach showed higher regional consistency and lower variability in T1w/T2w-derived myelin estimates (CV = 16.50% vs 40.56% in FastSurfer), with more spatially consistent thickness-myelin interaction patterns in artifact-prone ventral regions. Integrating FastSurfer into the HCP pipeline with hybrid T2w- and T1w-based masking enables stable cortical reconstruction by constraining signal-driven instability while preserving algorithm-dependent spatial organization. These findings highlight the importance of masking as a constraint on instability in cortical reconstruction and support the applicability of HCP-style analysis to clinical and legacy MRI datasets.

neuroscience↗

bioRxiv2024

Peristaltic pump-triggered amyloid formation suggests shear stresses are in vivo risk factors of amyloid nucleation

Amyloid fibrils, crystal-like fibrillar aggregates of denatured proteins, are formed linked with the breakdown of supersaturation, causing a series of amyloidosis including Alzheimers and Parkinsons diseases. Although varying in vitro factors are known, in vivo factors breaking supersaturation are unclear. We found that flowing by a peristaltic pump effectively triggers amyloid formation of hen egg white lysozyme, a model amyloidogenic protein, and, moreover, amyloidosis-associated proteins (i.e. -synuclein, amyloid {beta} 1-40, and {beta}2-microglobulin). The peristaltic pump-dependent amyloid formation was visualized by a fluorescence microscope with looped flow system, revealing dynamic motions under flow. Among them, amyloid fibrils of amyloid {beta} 1-40 were stickier than others, self-associating, absorbing to loop surfaces, and surging upon flicking the loop, implying early stages of cerebral amyloid angiopathy. On the other hand, {beta}2-microglobulin at a neutral pH showed unique two-step amyloid formation with an oligomeric trapped intermediate, which might mimic amyloid formation in patients. Peristalsis-caused strong shear stresses were considered to mechanically break supersaturation. Shearing stresses occur in vivo at varying levels, suggesting that they break otherwise persistent supersaturation, thus triggering amyloid formation and ultimately leading to amyloidosis. (182 words <200 words)

biophysics↗

bioRxiv2024

Glial scar formation by reactive astrocytes derived from oligodendrocyte progenitor cells after closed-head injury

The diversity of reactive astrocytes is key to understanding complicated pathological processes in the brain. The accumulation of reactive astrocytes expressing the neural stem/precursor cell marker Nestin is common after brain injury, but the pathological implications of this reactive astrocyte subpopulation remain elusive. This study initially aimed to determine the origin and fate of these reactive astrocytes expressing Nestin by characterizing cells labeled with green fluorescent protein (GFP) after closed-head injury, using a Nestin promoter region widely utilized to study neural stem/precursor cells. Unexpectedly, oligodendrocyte progenitor cells (OPCs), rather than astrocytes, were robustly and selectively labeled with GFP. A fraction of these cells showed a subsequent upregulation of astrocyte markers and were incorporated into glial scars. These glial scars are aggregates of reactive astrocytes that form between lesion cores and the perilesional recovering region. Deletion of the Stat3 gene, which is essential for astrocyte activation, using a Nestin promoter reduced glial scars, further confirming that OPCs are involved in glial scar formation. Reactive astrocytes labeled with a glial fibrillary acidic protein promoter differed in morphology and distribution from astrocytes derived from OPCs. This confirms that astrocytes and OPCs produce distinct reactive astrocyte subpopulations. Some GFP-labeled OPCs lacking astrocyte markers were found to distribute in perilesional recovering regions. The reduced expression of Nestin and OPC markers in these non-astrocytic descendants of OPCs, coupled with a significant fraction of these cells remaining olig2-positive, suggests that OPCs give rise to both reactive astrocytes and oligodendrocytes. These findings suggest that OPCs are activated by a novel process after brain injury.

neuroscience↗

bioRxiv2023

Myeloid Zfhx3 Deficiency Protects Against Hypercapnia-induced Suppression of Host Defense Against Influenza A Virus

Hypercapnia, elevation of the partial pressure of CO2 in blood and tissues, is a risk factor for mortality in patients with severe acute and chronic lung diseases. We previously showed that hypercapnia inhibits multiple macrophage and neutrophil antimicrobial functions, and that elevated CO2 increases the mortality of bacterial and viral pneumonia in mice. Here, we show that normoxic hypercapnia downregulates innate immune and antiviral gene programs in alveolar macrophages (AMOs). We also show that zinc finger homeobox 3 (Zfhx3), mammalian ortholog of zfh2, which mediates hypercapnic immune suppression in Drosophila, is expressed in mouse and human MOs. Deletion of Zfhx3 in the myeloid lineage blocked the suppressive effect of hypercapnia on immune gene expression in AMOs and decreased viral replication, inflammatory lung injury and mortality in hypercapnic mice infected with influenza A virus. Our results establish Zfhx3 as the first known mammalian mediator of CO2 effects on immune gene expression and lay the basis for future studies to identify therapeutic targets to interrupt hypercapnic immunosuppression in patients with advanced lung diseases. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/530480v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@f6f907org.highwire.dtl.DTLVardef@577795org.highwire.dtl.DTLVardef@6c0068org.highwire.dtl.DTLVardef@8ebb72_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2022

Apoplast-localized β-Glucosidase Elevates Isoflavone Accumulation in the Soybean Rhizosphere

Plant specialized metabolites (PSMs) are often stored as glycosides within cells and released from the roots with some chemical modifications. While isoflavones are known to function as symbiotic signals with rhizobia and to modulate the soybean rhizosphere microbiome, the underlying mechanisms of root-to-soil delivery are poorly understood. In addition to transporter-mediated secretion, the hydrolysis of isoflavone glycosides in the apoplast by an isoflavone conjugate-hydrolyzing {beta}-glucosidase (ICHG) has been proposed but not yet verified. To clarify the role of ICHG in isoflavone supply to the rhizosphere, we have isolated two independent mutants defective in ICHG activity from a soybean high-density mutant library. In the ichg mutants, the isoflavone contents and composition in the root apoplast and root exudate significantly changed. When grown in a field, the lack of ICHG activity considerably reduced isoflavone aglycone contents in roots and the rhizosphere soil, although the transcriptomes showed no distinct differences between the ichg mutants and WTs. Despite the change in isoflavone contents and composition of the root and rhizosphere of the mutants, root and rhizosphere bacterial communities were not distinctive from those of the WTs. Root bacterial communities and nodulation capacities of the ichg mutants did not differ from the WTs under nitrogen-deficient conditions, either. Taken together, these results indicate that ICHG elevates the accumulation of isoflavones in the soybean rhizosphere but is not essential in isoflavone-mediated plant-microbe interactions.

plant biology↗

bioRxiv2020

A model ecosystem of twelve cryopreservable microbial species allowing for a non-invasive approach

Simultaneous understanding of both individual and ecosystem dynamics is crucial in an era marked by the degradation of ecosystem services. Herein, we present a high-throughput synthetic microcosm system comprising 12 functionally and phylogenetically diverse microbial species. These species are axenically culturable, cryopreservable, and can be measured noninvasively via microscopy, aided by machine learning. This system includes prokaryotic and eukaryotic producers and decomposers, and eukaryotic consumers to ensure functional redundancy. Our model system displayed both positive and negative interspecific interactions and higher-order interactions that surpassed the scope of any two-species interaction. Although complete species coexistence was not our primary objective, we identified several conditions under which at least one species from the producers, consumers, and decomposers groups, and one functionally redundant species, persisted for over six months. These conditions set the stage for detailed investigations in the future. Given its designability and experimental replicability, our model ecosystem offers a promising platform for deeper insights into both individual and ecosystem dynamics, including evolution and species interactions.

microbiology↗

bioRxiv2020

SC-JNMF: Single-cell clustering integrating multiple quantification methods based on joint non-negative matrix factorization

AO_SCPLOWBSTRACTC_SCPLOWUnsupervised cell clustering is important in discovering cell diversity and subpopulations. Single-cell clustering using gene expression profiles is known to show different results depending on the method of expression quantification; nevertheless, most single-cell clustering methods do not consider the method. In this article, we propose a robust and highly accurate clustering method using joint non-negative matrix factorization (joint NMF) based on multiple gene expression profiles quantified using different methods. Matrix factorization is an excellent method for dimension reduction and feature extraction of data. In particular, NMF approximates the data matrix as the product of two matrices in which all factors are non-negative. Our joint NMF can extract common factors among multiple gene expression profiles by applying each NMF to them under the constraint that one of the factorized matrices is shared among the multiple NMFs. The joint NMF determines more robust and accurate cell clustering results by leveraging multiple quantification methods compared to the conventional clustering methods, which uses only a single quantification method. In conclusion, our study showed that our clustering method using multiple gene expression profiles is more accurate than other popular methods.

bioinformatics↗

bioRxiv2020

Visualizing ATP Dynamics in Live Mice

ABSTRACTAnalysis of the dynamics of adenosine triphosphate (ATP) is vital to quantitatively define the actual roles of ATP in biological activities. Here, we applied a genetically encoded Förster resonance energy transfer biosensor “GO-ATeam” and created a transgenic mouse model that allows systemic ATP levels to be quantitatively, sensitively, noninvasively, and spatiotemporally measured under physiological and pathological conditions. We used this model to readily conduct intravital imaging of ATP dynamics under three different conditions: during exercise, in all organs and cells; during myocardial infarction progression; and in response to the application of cardiotoxic drugs. These findings provide compelling evidence that the GO-ATeam mouse model is a powerful tool to investigate the multifarious functions of cellular ATP in vivo with unprecedented spatiotemporal resolution in real-time. This will inform predictions of molecular and morphological responses to perturbations of ATP levels, as well as the elucidation of physiological mechanisms that control ATP homeostasis.One Sentence Summary Intravital real-time imaging of ATP dynamics in multiple organs using GO-ATeam mice, can be used to quantitatively, sensitively, noninvasively, and spatiotemporally measure systemic ATP levels and provide a platform for preclinical pharmacological studies.Competing Interest StatementM.Yamamoto is involved in a pending patent related to GO-ATeam mice. H.I. holds a patent for ATeam probe. All other authors declare no competing interests.View Full Text

physiology↗

bioRxiv2020

Diurnal metabolic regulation of isoflavones and soyasaponins in soybean roots

Isoflavones and soyasaponins are major specialized metabolites accumulated in soybean roots and secreted into the rhizosphere. Unlike the biosynthetic pathway, the transporters involved in metabolite secretion remain unknown. The developmental regulation of isoflavone and soyasaponin secretions has been recently reported, but the diurnal regulation of their biosynthesis and secretion still needs to be further studied. To address these challenges, we conducted transcriptome and metabolite analysis using hydroponically grown soybean plants at 6-hour intervals for 48 hours in a 12-h-light/12-h-dark condition. Isoflavone and soyasaponin biosynthetic genes showed opposite patterns in the root tissues; that is, the former genes are highly expressed in daytime, while the latter ones are strongly induced at nighttime. GmMYB176 encoding a transcription factor of isoflavone biosynthesis was upregulated from ZT0 (6:00 am) to ZT6 (12:00 am), followed by the induction of isoflavone biosynthetic genes at ZT6. The isoflavone aglycone content in the roots accordingly increased from ZT6 to ZT18 (0:00 am), accompanied by an increase in glucoside levels that peaked at ZT0. The isoflavone aglycone content in root exudates was kept consistent throughout the day, whereas that of glucosides increased at ZT6, which reflected the decreased expression of the gene encoding beta-glucosidase involved in the hydrolysis of apoplast-localized isoflavone conjugates. Co-expression analysis revealed that those isoflavone and soyasaponin biosynthetic genes formed separate clusters, which exhibited a correlation to ABC and MATE transporter genes. As summary, the results in this study indicated the diurnal regulation of isoflavone biosynthesis in soybean roots and the putative transporter genes responsible for isoflavone and soyasaponin transport.

plant biology↗

bioRxiv2019

Morphological differences between phyllosoma larvae from the midwestern and eastern Pacific populations of the pronghorn spiny lobster Panulirus penicillatus

The pronghorn spiny lobster Panulirus penicillatus is known to have the widest distribution among palinurid lobster species, occurring in tropical and sub-tropical areas of the Indo-Pacific Ocean. In the Pacific Ocean, mitochondrial DNA analyses have revealed that the western-central and eastern populations are genetically isolated. We performed morphological investigations on mid- to late-stage phyllosoma larvae collected in these two areas. The larvae of the western-central population had a significantly narrower cephalic shield, shorter abdomen, and longer eyestalk than those of the eastern population. Additionally, for larvae larger than about 25-mm body length, the widest position of the cephalic shield in the western-central population was located closer to the middle of the median line of the cephalic shield than that in the eastern population. The ratio of width to length of cephalic shield and the ratio of cephalic shield width to thorax width are key traits for distinguishing between the larvae of the two populations.

ecology↗

bioRxiv2018

Screening for insulin-independent pathways that modulate glucose homeostasis identifies androgen receptor antagonists

Pathways modulating glucose homeostasis independently of insulin would open new avenues to combat insulin resistance and diabetes. Here, we report the establishment, characterization and employment of a vertebrate insulin-free model to identify insulin-independent modulators of glucose metabolism. insulin knockout zebrafish recapitulate core characteristics of diabetes and survive only up to larval stages. Utilizing a highly efficient endoderm transplant technique, we generated viable chimeric adults that provide the large numbers of insulin mutant larvae required for our screening platform. Using glucose as a disease-relevant readout, we screened 2233 molecules and identified 3 that consistently reduced glucose levels in insulin mutants. Most significantly, we uncovered an insulin-independent beneficial role for androgen receptor antagonism in hyperglycemia, mostly by reducing fasting glucose levels. Our study proposes therapeutic roles for androgen signaling in diabetes and, more broadly, offers a novel in vivo model for rapid screening and decoupling of insulin-dependent and -independent mechanisms.

developmental biology↗