Biology subjects

Nasu, M.

Publications and source records attributed to Nasu, M..

8 recordsLinked to original sources

bioRxiv2026

A conserved lamination pattern in the paleocortex and the neocortex revealed by single-cell RNA analyses

The piriform cortex, the largest paleocortical domain and a central olfactory cortex, is classically described as a three-layered structure, with layer II subdivided into semilunar and superficial pyramidal neurons. However, its cellular composition, developmental logic, and evolutionary relationship with the six-layered neocortex remain incompletely defined. Here, we aimed to resolve piriform cortical cell types and laminar organization and compare their molecular programs across mammalian cortical regions and the reptilian cortex. We performed single-nucleus RNA sequencing of the microdissected piriform cortex and integrated neuronal lineage data with published datasets, with spatial validation via the Allen Mouse Brain Atlas. Interspecies analyses identified piriform-dominant glutamatergic populations marked by Unc13c/Lmo3/Rora and an Rorb/Reln/Ntng1-enriched sensory-recipient subtype localized to the superficial layer IIa, consistent with semilunar neurons. Spatial transcriptomic mapping revealed that piriform layer IIb contains neocortical upper-layer-like corticocortical neurons, while piriform layer III segregates into layer V-like (IIIa), layer VI-like (IIIb), and VIb/VII (subplate)-equivalent populations, indicating a neocortex-like laminar framework with an inverted positioning of sensory recipients and corticocortical compartments relative to the neocortex. GABAergic neurons largely conformed to canonical MGE- and CGE-derived lineages but included a piriform-specific Rgs9+Pde7b+ subtype consistent with an LGE-related origin, suggesting region-specific diversification of GABAergic neurons. Disease ontology enrichment linked hippocampus-dominant glutamatergic programs to Alzheimers-related genes and piriform-dominant (and pan-cortical) excitatory and inhibitory programs to autism spectrum disorder and intellectual disability, implicating coordinated E/I circuit specializations in area-selective vulnerability. These findings support a revised view of the paleocortex as a divergent specialization of a conserved, multilayered cortical program and provide molecular markers and a comparative framework for studying cortical evolution and region-specific disease susceptibility.

developmental biology↗

bioRxiv2025

f4-statistics-based ancestry profiling and convolutional neural network phenotyping shed new light on the structure of genetic and spike shape diversity in Aegilops tauschii Coss.

Aegilops tauschii Coss., a progenitor of bread wheat, is an important wild genetic resource for breeding. The species comprises three genetically defined lineages (TauL1, TauL2, and TauL3), each displaying distinctive phenotypes in various agronomic traits, including spike shape. In the present work, we studied the relationship between population structure and spike shape variation patterns using a collection of 249 accessions. f4-statistics-based ancestry profiling confirmed the previously identified lineages and revealed a genetic component derived from TauL3 in the genomes of some southern Caspian and Transcaucasus TauL1 and TauL2 accessions. Spike shape variation patterns were analyzed using a convolutional neural network-based approach, trained on green and dry spike image datasets. This analysis showed that spike shape diversity is structured according to lineages and demonstrated that the lineages can be distinguished based on spike shape. The implications of these findings for the origins of common wheat and the intraspecific taxonomy of Ae. tauschii are discussed. Plain Language SummaryWild wheat, Aegilops tauschii, represents a vast reservoir of alleles that have not yet been utilized in breeding. These alleles may confer beneficial phenotypes, such as drought tolerance and disease resistance, when introduced into bread wheat. To fully leverage this reservoir, it is essential to quickly identify strains with potentially useful alleles. In Ae. tauschii, which consists of strain groups (lineages) with unique genetic makeups, this can be done by determining a strains lineage based on spike shape. In this work, we trained machine learning models for this purpose and found that spike shape diversity reflects lineage structure. These models demonstrated potential for practical use in assigning strains to their respective lineages based on spike shape. Our work opens new avenues for the application of machine learning in wheat improvement, as well as in the genetic and evolutionary studies of wheat morphology.

evolutionary biology↗

bioRxiv2023

sRNAfrag: A pipeline and suite of tools to analyze fragmentation in small RNA sequencing data

Fragments derived from small RNAs such as small nucleolar RNAs hold biological relevance. However, they remain poorly understood, calling for more comprehensive methods for analysis. We developed sRNAfrag, a standardized workflow and set of scripts to quantify and analyze sRNA fragmentation of any biotype. In a benchmark, it is able to detect loci of mature microRNAs fragmented from precursors and, utilizing multi-mapping events, the conserved 5 seed sequence of miRNAs which we believe may extraoplate to other small RNA fragments. The tool detected 1411 snoRNA fragment conservation events between 2/4 eukaryotic species, providing the opportunity to explore motifs and fragmentation patterns not only within species, but between. Availability: https://github.com/kenminsoo/sRNAfrag.

bioinformatics↗

bioRxiv2023

Eosinophils exert direct and indirect anti-tumorigenic effects in the development of esophageal squamous cell carcinoma

Background/AimsEosinophils are present in several solid tumors and have context-dependent function. Our aim is to define the contribution of eosinophils in esophageal squamous cell carcinoma (ESCC), since their role in ESCC is unknown. MethodsEosinophils were enumerated in tissues from two ESCC cohorts. Mice were treated with 4-nitroquinolone-1-oxide (4-NQO) for 8 weeks to induce pre-cancer or 16 weeks to induce carcinoma. Eosinophil number was modified by monoclonal antibody to IL-5 (IL5mAb), recombinant IL-5 (rIL-5), or genetically with eosinophil-deficient ({Delta}dblGATA) mice or mice deficient in eosinophil chemoattractant eotaxin-1 (Ccl11-/-). Esophageal tissue and eosinophil specific RNA-sequencing was performed to understand eosinophil function. 3-D co-culturing of eosinophils with pre-cancer or cancer cells was done to ascertain direct effects of eosinophils. ResultsActivated eosinophils are present in higher numbers in early stage versus late stage ESCC. Mice treated with 4-NQO exhibit more esophageal eosinophils in pre-cancer versus cancer. Correspondingly, epithelial cell Ccl11 expression is higher in mice with pre-cancer. Eosinophil depletion using three mouse models (Ccl11-/- mice, {Delta}dblGATA mice, IL5mAb treatment) all display exacerbated 4-NQO tumorigenesis. Conversely, treatment with rIL-5 increases esophageal eosinophilia and protects against pre-cancer and carcinoma. Tissue and eosinophil RNA-sequencing revealed eosinophils drive oxidative stress in pre-cancer. In vitro co-culturing of eosinophils with pre-cancer or cancer cells resulted in increased apoptosis in the presence of a degranulating agent, which is reversed with N-acetylcysteine, a reactive oxygen species (ROS) scavenger. {Delta}dblGATA mice exhibited increased CD4 T cell infiltration, IL-17, and enrichment of IL-17 pro-tumorigenic pathways. ConclusionEosinophils likely protect against ESCC through ROS release during degranulation and suppression of IL-17.

cancer biology↗

bioRxiv2021

Pseudoautosomal gene SHOX exhibits sex-biased random monoallelic expression and contributes to sex difference in height

Adult men are, on average, [~]13 cm taller than adult women. Although previous studies have suggested a significant contribution of sex chromosomal genes to sexual dimorphism in height, all attempts to identify a male-specific growth gene have failed. In the present study, we analyzed transcripts from cartilage tissues, and found that the expression of SHOX, a growth-promoting gene in the pseudoautosomal region on the X and Y chromosomes, was lower in females than in males. DNA methylation analyses showed that SHOX has some characteristics of genes subjected to X chromosome inactivation (XCI). These findings indicate that sex difference in human height is mainly ascribed to incomplete spreading of XCI on a pseudoautosomal gene. More importantly, RT-PCR of fibroblast clones revealed XCI-independent random clonal monoallelic expression of SHOX. We presume that during eutherian evolution, SHOX translocated from an autosome to the proto-sex chromosome without losing the epigenetic memory of random clonal monoallelic expression and subsequently underwent partial XCI. This study provides a novel model of epigenetic gene regulation leading to phenotypic diversity in humans.

genetics↗

bioRxiv2020

The SEQC2 Epigenomics Quality Control (EpiQC) Study: Comprehensive Characterization of Epigenetic Methods, Reproducibility, and Quantification

Cytosine modifications in DNA such as 5-methylcytosine (5mC) underlie a broad range of developmental processes, maintain cellular lineage specification, and can define or stratify cancer and other diseases. However, the wide variety of approaches available to interrogate these modifications has created a need for harmonized materials, methods, and rigorous benchmarking to improve genome-wide methylome sequencing applications in clinical and basic research. Here, we present a multi-platform assessment and a global resource for epigenetics research from the FDAs Epigenomics Quality Control (EpiQC) Group. The study design leverages seven human cell lines that are designated as reference materials and publicly available from the National Institute of Standards and Technology (NIST) and Genome in a Bottle (GIAB) consortium. These samples were subject to a variety of genome-wide methylation interrogation approaches across six independent laboratories, with a primary focus was on 5-methylcytosine modifications. Each sample was processed in two or more technical replicates by three whole-genome bisulfite sequencing (WGBS) protocols (TruSeq DNA methylation, Accel-NGS MethylSeq, and SPLAT), oxidative bisulfite sequencing (TrueMethyl), one enzymatic deamination method (EMseq), targeted methylation sequencing (Illumina Methyl Capture EPIC), and single-molecule long-read nanopore sequencing from Oxford Nanopore Technologies. After rigorous quality assessment and comparison to Illumina EPIC methylation microarrays and testing on a range of algorithms (Bismark, BitmapperBS, BWAMeth, and GemBS), we found overall high concordance between assays (R=0.87-R0.93), differences in efficency of read mapping and CpG capture and coverage, and platform performance. The data provided herein can guide continued used of these reference materials in epigenomics assays, as well as provide best practices for epigenomics research and experimental design in future studies.

genomics↗

bioRxiv2019

Gorlin syndrome-induced pluripotent stem cells form medulloblastoma with loss of heterozygosity in PTCH1

Gorlin syndrome is a rare autosomal dominant hereditary disease with high incidence of tumors such as basal cell carcinoma and medulloblastoma. Disease-specific induced pluripotent stem cells (iPSCs) have now been used as a model to analyze disease pathogenesis as well as an animal model. In this study, we generated iPSCs derived from fibroblasts of four patients with Gorlin syndrome (Gln-iPSCs) with a heterozygous mutation of the PTCH1 gene. Gln-iPSCs from the four patients developed medulloblastoma in 100% (four out of four), a manifestation of Gorlin syndrome, in the teratomas after implantation into immunodeficient mice, but none (0/584) of the other iPSC-teratomas. One of the medulloblastomas had loss of heterozygosity in the PTCH1 gene while benign teratoma, i.e. non-medulloblastoma part, did not, indicating a close clinical correlation between tumorigenesis in Gorlin syndrome patients and Gln-iPSCs.

cell biology↗

bioRxiv2016

Pharmaceutical efficacy of human epiphyseal chondrocytes with differential replication numbers for cellular therapy products

The cell-based therapy for cartilage or bone requires a large number of cells serial passages of chondrocytes are, therefore, needed. However, fates of expanded chondrocytes from extra fingers remains unclarified. The chondrocytes from human epiphyses morphologically changed from small polygonal cells, to bipolar elongated spindle cells and to large polygonal cells with degeneration at early passages. Gene of type II collagen was expressed in the cells only at a primary culture (Passage 0) and Passage 1 (P1) cells. The nodules by implantation of P0 to P8 cells were composed of cartilage and perichondrium. The cartilage consisted of chondrocytes with round nuclei and type II collagen-positive matrix, and the perichondrium consisted of spindle cells with type I collage-positive matrix. The cartilage and perichondrium developed to bone with marrow cavity through enchondral ossification. Chondrogenesis and osteogenesis by epiphyseal chondrocytes depended on replication number in culture. It is noteworthy to take population doubling level in correlation with pharmaceutical efficacy into consideration when we use chondrocytes for cell-based therapies.

cell biology↗