Biology subjects

Matsui, S.

Publications and source records attributed to Matsui, S..

7 recordsLinked to original sources

bioRxiv2026

Intrinsic-like blood coagulation activity in fish: Involvement of hepatocyte growth factor activator and interspecific diversity

Most fish lack identifiable orthologs of factor XII and other components of the mammalian contact system; however, their plasma exhibits coagulation responses to negatively charged surfaces. Therefore, hepatocyte growth factor activator (HGFA), an evolutionary relative of factor XII, has been proposed as an initiator of factor XII-independent, contact activation-like coagulation in fish. To examine the distribution of this activity, we compared plasma from multiple fish species using an activated partial thromboplastin time (aPTT)-like assay. Thrombin substrate-cleaving activity was detected under aPTT-like conditions in multiple species lacking identifiable factor XII orthologs, demonstrating that factor XII-independent intrinsic pathway-like activity is broadly distributed among fish. To assess the involvement of factor XII- or HGFA-related proteases, we performed inhibitor assays. The observed inhibitor sensitivities did not consistently support HGFA as the principal initiator of the activity. We next compared the occurrence and intensity of the activity with the genomic presence and domain organization of HGFA orthologs. Neither the presence nor the magnitude of the activity closely corresponded to HGFA occurrence or structure; notably, activity was detected in bichir, in which no clear HGFA ortholog has been identified. Finally, comparative domain analysis showed that fish HGFA generally lacks several structural features associated with the surface-dependent autoactivation of mammalian factor XII. These findings indicate that factor XII-independent, contact activation-like coagulation is broadly present in fish but cannot be explained solely by HGFA. Fish may therefore possess diverse or unidentified proteolytic mechanisms that initiate coagulation under aPTT-like conditions, providing insights into the evolutionary emergence of the vertebrate contact system.

biochemistry↗

bioRxiv2026

Combinatorial pioneer transcription factor binding reinforces bivalent epigenetic states to preserve lineage fidelity

Cooperative and collaborative modes of transcription factor (TF) binding are central to eukaryotic gene activation, providing regulatory specificity and robustness in cell fate control. However, gene activation is only half the story of transcriptional regulation, and cells also require mechanisms to repress inappropriate gene programs. It remains largely unknown how broadly expressed repressive TFs and epigenetic regulators achieve context-specific repression required for proper cell differentiation. Here, we show that the repressive TF PRDM1 cooperates with lineage- and stage-specific pioneer TFs during human endoderm differentiation. Notably, the number of diverse pioneer TFs bound at enhancers determines the strength of PRDM1-mediated enhancer repression. Mechanistically, collaborative binding by multiple pioneer TFs synergistically promotes local nucleosome remodeling and stabilizes PRDM1 occupancy, culminating in the formation of hyper-bivalent enhancers that are characterized by strongly elevated levels of H3K4me1 and Polycomb-associated modifications. These enhancers reinforce the repression of alternative-lineage, and past and future developmental programs. Together, our findings redefine the roles of TF cooperation and chromatin accessibility beyond the prevailing activation-centric view. We propose a collaborative repression model in which diverse pioneer TFs establish focal chromatin accessibility that reinforces the context-specific assembly of repressive regulators, thereby safeguarding lineage and developmental fidelity.

genomics↗

bioRxiv2025

MAPK/ERK signaling blocks ectopic H3K9me3 heterochromatin formation to confer mesoderm and endoderm developmental competence

During gastrulation, dynamic interplay among cell signaling pathways dictates cell fate decisions. While extensive studies have elucidated their critical roles in morphological regulation, how these signals orchestrate the epigenome to confer developmental competence remains unclear. In this study, we demonstrate that H3K9me3-marked facultative heterochromatin domains undergo global reorganization during differentiation of human pluripotent stem cells into mesoderm and endoderm, which arise through epithelial-mesenchymal transition (EMT), but not into ectoderm, which retains epithelial state. We identify the MAPK/ERK pathway, acting downstream of FGF signaling, as a key mediator of this reorganization. Specifically, the MAPK/ERK pathway prevents ectopic formation of H3K9me3 domains at EMT- and lineage-specific gene loci whose expression is necessary for mesoderm and endoderm differentiation. Collectively, our findings reveal a previously unrecognized role for MAPK/ERK signaling in reorganizing the H3K9me3 landscape to enable mesoderm and endoderm differentiation, bridging a critical gap in our knowledge of how cell signaling pathways shape the epigenetic landscape during development.

developmental biology↗

bioRxiv2022

Pioneer transcription factors coordinate active and repressive gene expression states to regulate cell fate

Pioneer transcription factors (TFs) regulate cell fate by establishing transcriptionally primed and active states. However, cell fate control requires the coordination of both lineage-specific gene activation and repression of alternative lineage programs, a process that is poorly understood. Here, we demonstrate that the pioneer TF Forkhead box A (FOXA), required for endoderm lineage commitment, coordinates with the PR domain zinc finger 1 (PRDM1) TF to recruit Polycomb repressive complexes, which establish bivalent enhancers and repress alternative lineage programs. Similarly, the pioneer TF OCT4 coordinates with PRDM14 to repress cell differentiation programs in pluripotent stem cells, suggesting this is a common feature of pioneer TFs. We propose that pioneer and PRDM TFs coordinate recruitment of Polycomb complexes to safeguard cell fate. One-Sentence SummaryPioneer and PRDM transcription factors repress alternative lineage programs.

cell biology↗

bioRxiv2021

High permeability of the CSF flow in the juvenile mouse brain by brain-wide DCE-MRI

The vasculature system with a lymphatic function in the brain is manifested as meningeal lymphatic vessels and the glymphatic system, which drain waste products from cerebrospinal fluid (CSF) and produce interstitial fluid. Invasion of stimulated immune cells or inflammatory cytokines during the maturation is regarded as a sign of the disruption of brain functions through excessive immune stresses. However, it is unclear when the lymphatic system is functionally completed and in which parts of the organ the brain immunity is privileged (i.e., the blood-brain barrier is fully established). Here, we visualized the whole-head signal of gadolinium (Gd) contrast agents in mouse brains to investigate the CSF flow from the signals of Gd-contrast agents using magnetic resonance imaging (MRI) in the course of developmental stages. We found higher Gd-signals in the olfactory bulbs, prefrontal cortex, parietal surface regions of the neocortex along with dorsal meningeal lymphatic vessels, ventral midbrain, and a part of cerebellum, as well as in the basal brain regions, at the immature stage of postnatal (P) 4 weeks, compared to the P8-12 weeks. Our results suggest that the barrier of the vasculature system in mouse brains is still permeable until P1-month and small molecules can leak into the parenchyma.

neuroscience↗

bioRxiv2020

Examining the genetic influences of migratory status on island colonisation by naturally and recently established populations of a bird species

AimFounder effects and recurrent immigration are two major factors that potentially contribute to genetic differentiation and population persistence in the early-stage of remote island colonization. However, their relative importance remains controversial. By conducting population genetics analyses of multiple remote island populations of the bull-headed shrike established naturally within several decades, we examined the relative contributions of founder effects and recurrent immigration on these island populations. LocationJapan TaxonLanius bucephalus MethodsWe used 15 microsatellite loci to analyze the population genetics of four newly established island populations and five Japanese mainland populations. Allelic richness, heterozygosity, genetic differentiation, and the strength of the genetic bottleneck were compared among the islands. Two analyses, STRUCTURE and the DAPC, were conducted to assess the relative influence of founder effects and recurrent immigration on genetic differentiation. Temporal samples collected over eight years on Minami-Daito Island were used to detect any change in genetic structure due to recurrent immigration. ResultsThe founder effect strongly influenced genetic differentiation on the most remote oceanic island, Chichi-jima Island. However, this population became extinct 20 years after colonization, possibly owing to a lack of recurrent immigration. The founder effect moderately influenced a land-bridge island, Kikai-jima Island, indicating the presence of a relatively large founder population without recurrent immigration. Surprisingly, another distant oceanic island, Minami-Daito Island, was likely subject to multiple recurrent immigration events from the mainland, which obscured any genetic differentiation previously established by the founder effect. Main conclusionUnderlying the island-specific population dynamics of colonization, founder effects contributed to the genetic differentiation among the three studied island populations. Importantly, however, recurrent immigration strongly affected the population persistence and subsequent evolutionary processes of remote island populations, potentially overwhelming the founder effect. We argue the importance of recurrent immigration in highly remote island colonization, which has been previously overlooked.

ecology↗

bioRxiv2016

Empirical Bayes estimation of semi-parametric hierarchical mixture models for unbiased characterization of polygenic disease architectures

Genome-wide association studies (GWAS) suggest that the genetic architecture of complex diseases consists of unexpectedly numerous variants with small effect sizes. However, the polygenic architectures of many diseases have not been well characterized due to lack of simple and fast methods for unbiased estimation of the underlying proportion of disease-associated variants and their effect-size distribution. Applying empirical Bayes estimation of semi-parametric hierarchical mixture models to GWAS summary statistics, we confirmed that schizophrenia was extremely polygenic ([~] 40% risk variants of independent genome-wide SNPs, most within odds ratio (OR)=1.03), whereas rheumatoid arthritis was less polygenic ([~] 4 to 8% risk variants, significant portion reaching OR=1.05 to 1.1). For rheumatoid arthritis, stratified estimations revealed that expression quantitative loci in blood explained large genetic variance, and low- and high-frequency derived alleles were prone to be risk and protective, respectively, suggesting a predominance of deleterious-risk and advantageous-protective mutation. Despite genetic correlation, effect-size distributions for schizophrenia and bipolar disorder differed across allele frequency. These analyses distinguished disease polygenic architectures and provided clues for etiological differences in complex diseases.

genomics↗