Biology subjects

Takeo, Y.

Publications and source records attributed to Takeo, Y..

6 recordsLinked to original sources

bioRxiv2026

Multicellular Spatial Programs Define the Histopathological Architecture of Meningioma

Tumors are often described by cell types or gradients, but the organizing units of tumor tissue remain unclear. Using meningiomas, which show marked morphologic diversity despite constrained and recurrent genetics, we identify reproducible multicellular spatial molecular programs (SMPs) characterized by recurring cell-type mixtures that combine in different proportions across tumors. We built a multi-omic atlas of 147 human meningiomas (1.6 million cells/spots), integrating scRNA-seq, Visium, CosMx-RNA, and CosMx-Protein. Across platforms, SMPs mapped onto canonical whorl-lobule architecture and defined a structured ecological landscape linking hypoxic, immune-evasive states to vascularized, matrix-remodeling, and mineralization-rich states. For translation, we developed MeningNet, a hybrid ConvNeXt-Vision Transformer that infers SMPs directly from hematoxylin-and-eosin sections. MeningNet generalized across an internal replication cohort and 465 external whole-slide images, recovering cross-platform inference and showing significant association with CNS-WHO grade. These findings establish meningioma architecture as a reproducible histopathological framework for inferring spatial molecular state from routine pathology.

Cancer Biology↗

bioRxiv2025

Wakeful targeted memory reactivation during short rest periods modulates motor learning via the lateral orbitofrontal cortex network

This study investigated whether wakeful targeted memory reactivation (TMR) during short rest intervals improves motor learning. Participants were randomly assigned to the following four groups and performed a sequential key-press task under each condition: (1) TMRno group: no auditory stimuli, (2) TMRregular group: auditory cues played at the same speed as the previous task, (3) TMRfast group: auditory cues played 1.3 times faster, and (4) TMRrandom group: auditory cues randomized in pitch. The TMRregular group suppressed early learning gains compared with the TMRno and TMRfastgroups. Electroencephalogram revealed reduced functional connectivity centered on the lateral orbitofrontal cortex (lOFC) in the TMRregular group. In contrast, the TMRfastgroup preserved early learning and exhibited improved lOFC-centered functional connectivity compared with the TMRregulargroup. Therefore, wakeful TMR might either hinder or support motor learning, depending on cue timing and structure, emphasizing the need to optimize sensory parameters for effective learning improvement.

neuroscience↗

bioRxiv2025

Golgi-associated nuclear import receptor importin-7 targets HPV from the Golgi to the nucleus to promote infection

During human papillomavirus (HPV) entry, the virus exploits COPI-dependent retrograde transport to cross the trans-Golgi network and Golgi stacks before reaching the nucleus to cause infection. How HPV enters the nucleus after exiting the Golgi is unclear, although mitotic nuclear envelop breakdown (NEB) appears important. Here we show that importin-7 (IPO7), a nuclear pore import receptor, associates with the Golgi and promotes HPV infection. Upon IPO7 knockdown, HPV infection is inhibited and the virus accumulates in the Golgi but does not enter the nucleus, demonstrating that IPO7 promotes Golgi-to-nucleus transport of HPV. We further reveal that the C-terminus of HPV capsid protein L2, which is thought to contain overlapping nuclear localization and cell-penetrating peptide sequences, binds directly to IPO7 in a step that requires COPI-dependent virus trafficking. Together these data identify a role of an importin in HPV infection, raising the possibility that the canonical nuclear pore import machinery plays an unanticipated role in NEB-dependent nuclear entry. TeaserHPV, a cancer-causing human pathogen, exploits the Golgi-associated nuclear import receptor IPO7 for Golgi-to-nucleus trafficking to promote infection.

cell biology↗

bioRxiv2024

γ-secretase facilitates retromer-mediated retrograde transport

The retromer complex mediates retrograde transport of protein cargos from endosomes to the trans-Golgi network (TGN). {gamma}-secretase is a multisubunit protease that cleaves the transmembrane domain of its target proteins. Mutations in genes encoding subunits of retromer or {gamma}-secretase can cause familial Alzheimer disease (AD) and other degenerative neurological diseases. It has been reported that retromer interacts with {gamma}-secretase, but the consequences of this interaction are not known. Here, we report that retromer-mediated retrograde protein trafficking in cultured human epithelial cells is impaired by inhibition of {gamma}-secretase activity or by genetic elimination of {gamma}-secretase. {gamma}-secretase inhibitor XXI and knockout of PS1, the catalytic subunit of {gamma}-secretase, inhibit endosome to TGN trafficking of retromer-dependent retrograde cargos, divalent metal transporter 1 isoform II (DMT1-II), cation-independent mannose-6-phosphate receptor (CIMPR), and shiga toxin. Trafficking of retromer-independent cargos, such as cholera toxin and a CIMPR mutant that does not bind to retromer was not affected by {gamma}-secretase inhibition. XXI treatment and PS1 KO inhibit interaction of {gamma}-secretase with retromer but do not inhibit the association of cargo with retromer or with {gamma}-secretase in intact cells. Similarly, these treatments do not affect the level of Rab7-GTP, which regulates retromer-cargo interaction. These results suggest that the {gamma}-secretase-retromer interaction facilitates retromer-mediated retrograde trafficking.

cell biology↗

bioRxiv2022

spARC Recovers Human Glioma Spatial SignalingNetworks with Graph Filtering

Biological networks operate within architectural frameworks that influence the state and function of cells through niche-specific factors such as exposure to nutrients and metabolites, soluble signaling molecules, and direct cognate cell-cell communication. Spatial omics technologies incorporate environmental information into the study of biological systems, where the spatial coordinates of cells may directly or indirectly encode these micro-anatomical features. However, they suffer from technical artifacts, such as dropout, that impede biological discovery. Current methods that attempt to correct for this fail to adequately integrate highly informative spatial information when recovering gene expression and modelling cell-cell dynamics in situ. To address this oversight, we developed spatial Affinity-graph Recovery of Counts (spARC), a data diffusion-based filtration method that shares information between neighboring cells in tissue and related cells in expression space, to recover gene dynamics and simulate signalling interactions in spatial transcriptomics data. Following validation, we applied spARC to 10 IDH-mutant surgically resected human gliomas across WHO grades II-IV in order to study signaling networks across disease progression. This analysis revealed co-expressed genes that border the interface between tumor and tumor-infiltrated brain, allowing us to characterize global and local structure of glioma. By simulating paracrine signaling in silico, we identified an Osteopontin-CD44 interaction enriched in grade IV relative to grade II and grade III astrocytomas, and validated the clinical relevance of this signaling axis using TCGA.

bioinformatics↗

bioRxiv2022

Microcephaly-associated WDR62 mutations hamper Golgi apparatus-to-spindle pole shuttling in human neural progenitors

WDR62 is a spindle pole-associated scaffold protein with pleiotropic functions during corticogenesis. Recessive mutations in WDR62 are associated with structural brain abnormalities and account for the second most common cause of autosomal recessive primary microcephaly (MCPH), indicating WDR62 as a critical hub for human brain development. Here, we investigated a C-terminal truncating mutation (D955AfsX112) in WDR62 using induced pluripotent stem cells (iPSCs) obtained from a patient with MCPH2. We generated neuroepithelial stem (NES) cells and cerebro-cortical progenitors and neurons from patient-derived and isogenic retro-mutated iPSC lines. We found that WDR62 dysfunction resulted in impaired cell cycle progression and alterations of the neurogenic trajectories of iPSC neuroderivatives. Moreover, we report WDR62 localization at the Golgi apparatus during interphase, both in human neural progenitors in vitro and in human fetal brain tissue. WDR62 shuttling from the Golgi apparatus to spindle poles is dynamic and microtubule-dependent. Impairment of WDR62 function and localization results in severe neurodevelopmental abnormalities, thus delineating new mechanisms in MCPH etiology.

neuroscience↗