Biology subjects

Koike, K.

Publications and source records attributed to Koike, K..

5 recordsLinked to original sources

bioRxiv2025

High-quality genome assembly and functional annotation of Hiroshima-derived Pacific oyster Magallana gigas

The Pacific oyster (Magallana gigas) is a widely distributed marine bivalve of major importance in aquaculture and is abundant along the Asian coasts. The Hiroshima Prefecture is the principal region for oyster production in Japan. The currently available reference genomes are derived from oysters of UK origin and do not fully capture the genetic characteristics of the Hiroshima populations. Here, we present a high-quality genome assembly and functional annotation of M. gigas from Hiroshima, Japan. The genome was assembled using PacBio HiFi long reads. After assembly, the contaminant contigs were removed, yielding a final assembly with a total length of 707 Mb, contig N50 of 7.9 Mb, and BUSCO completeness of 99.9 %. Of the 44,639 predicted protein-coding genes identified using GALBA, 43,806 were successfully annotated using a functional annotation workflow (Fanflow). Overall, the high-quality assembly and annotation provide a valuable genomic resource for exploring the genetic diversity and environmental adaptations of Hiroshima oyster populations. The data will facilitate future studies in breeding, functional genomics, and genome editing.

genomics↗

bioRxiv2025

Aberrant Hippo-YAP/TEAD signaling drives malignant transcriptional reprogramming in external auditory canal squamous cell carcinoma

PurposeExternal auditory canal squamous cell carcinoma (EACSCC) is an extremely rare malignancy. The molecular characteristics and evidence-based therapeutic strategies of EACSCC still remain to be elucidated. Experimental DesignComprehensive analyses of RNA sequencing (RNA-seq) and ChIP sequencing (ChIP-seq) utilizing YAP and H3K27Ac antibodies were performed in primary EACSCC and noncancerous ear skin samples. Functional experiments were performed in EACSCC-derived cells and Head and Neck Squamous Cell Carcinoma (HNSCC) cells in vitro and in vivo. Immunohistochemical staining of primary EACSCC tissues as well as survival analysis were conducted. ResultsRNA-seq indicated hyperactivation of YAP/TEAD-mediated transcriptional programs in EACSCC. H3K27Ac ChIP-seq suggested gained accessibility for transcription factor (TF) binding sites for TEAD, AP-1 and PITX TFs in EACSCC, and presence of EACSCC-specific super enhancers (SEs). YAP-bound SEs were involved in oncogenic transcription, including EGFR signaling. Small molecule TEAD inhibitor (smTEADi) VT104 showed significant suppression of proliferation and clonogenicity in EACSCC cells. Importantly, smTEADi not only inhibited YAP-TEAD interaction but also induced YAP-PITX2 binding, suggesting that PITX2 could represent an alternative partner TF of YAP under TEAD-inhibited conditions. Knockdown of PITX2 inhibited cell growth and migration of EACSCC and HNSCC cells, whereas overexpression of PITX2 induced expression of cell cycle, stemness, and EMT genes, as well as YAP/TAZ-TEAD target genes, and promoted tumor growth in vivo. Nuclear YAP and PITX2 expression were significantly correlated with poor prognosis of EACSCC patients. ConclusionsThis study highlighted the hyperactivation of the YAP-TEAD/PITX2 transcriptional program and its potential as a therapeutic target in EACSCC. Translational RelevanceExternal auditory canal squamous cell carcinoma (EACSCC) is an extremely rare malignancy related to chronic tissue damage and inflammation. Due to its rarity, the molecular characteristics of EACSCC are poorly understood, and evidence-based therapeutic strategies are not fully developed. Here, we provide evidence of hyperactivation of YAP/TEAD-driven transcriptional programs in EACSCC, utilizing comprehensive analyses of RNA-seq and YAP/H3K27Ac ChIP-seq in clinical tissue samples, as well as in vitro and in vivo experiments. In addition, our data suggest that the PITX2 transcription factor (TF) could represent an alternative partner TF of YAP under TEAD-inhibited conditions, which may rescue oncogenic transcription of TEAD. Importantly, YAP and PITX2 are co-expressed in EACSCC and predict poor prognosis of EACSCC patients. Our results provide a rationale for YAP-hyperactivation in EACSCC and contribute to a better understanding of this malignancy and the development of new therapeutic strategies.

cancer biology↗

bioRxiv2024

Excessive F-Actin and Microtubule Formation Mediates Primary Cilia Shortening and Loss in Response to Increased Extracellular Osmotic Pressure

The primary cilium is a small organelle protruding from the cell surface and is recognized as an antenna for signals from the extracellular milieu. Maintenance of primary cilia structure is crucial for proper behaviors of cells, tissues, and organs. While a dozen of studies have reported that several genetic factors impair the structure of primary cilia, evidence for environmental stimuli affecting primary cilia structures is limited. Here, we investigated an extracellular stress that affected primary cilia morphology and its underlying mechanisms. Hyperosmotic shock with increased extracellular sodium chloride concentration induced shortenings and disassembly of primary cilia in murine intramedullary collecting ducts cells. The shortening of primary cilia caused by hyperosmotic shock followed a loss of axonemal microtubules and delocalization of pericentriolar materials (PCMs). The primary cilia shortening/disassembly and PCMs delocalization were reversible. In parallel with these hyperosmotic shock-induced changes of primary cilia and PCMs, excessive microtubule and F-actin formation occurred in the cytoplasm. A microtubule-disrupting agent, Nocodazole, prevented the hyperosmotic shock-induced primary cilia disassembly partially, while preventing the delocalization of PCMs almost 100%. An actin polymerization inhibitor, Latrunculin A, also prevented partially the hyperosmotic shock-induced primary cilia shortening and disassembly, while preventing the delocalization of PCMs almost 100%. Taken together, we demonstrate that hyperosmotic shock induces reversible morphological changes in primary cilia and PCMs in a manner dependent on excessive formation of microtubule and F-actin.

cell biology↗

bioRxiv2021

Gross anatomy of the gluteal and posterior thigh muscles in koalas based on their innervations

There are not many descriptions of the muscle morphology of marsupials, despite the fact that they should show diversity according to the adaptation and dispersal to a variety of environments. Most of the previous studies regarding the gross anatomy of marsupials were conducted in the 1800 - 1900s, and many issues still remain that need to be reexamined. For instance, the muscle identification had been performed based only on their attachments and thus, muscle descriptions are often inconsistent among the studies. These classic studies often do not include figures or photographs, so the discrepancies in the descriptions of the muscles could only be verified by performing the muscle identification again with a more reliable method. This problem can be solved by performing muscle identification by innervation. This method, which focuses on the ontogenic origin of the muscle as opposed to the attachment site, is prone to individual and interspecies variation and is a common technique in recent anatomical research. This technique is more reliable than previous methods and is suitable for comparison with other taxa (i.e., eutherians). In this study, we first conducted muscle identification based on innervation in the gluteal and posterior thighs of koalas in order to reorganize the anatomical knowledge of marsupials. This is because the gluteus and posterior thighs of koalas are the areas where previous studies have been particularly inconsistent. We dissected five individual koalas and clarified discrepancies in previous studies, as well as investigated the unique muscle morphology and their function in koalas. Specifically, the koalas gluteal muscle group is suitable for abduction, while the posterior thigh muscles are particularly suitable for flexion. In the future, we will update the anatomical findings of marsupials in the same way to clarify the adaptive dissipation process of marsupials, as well as to contribute to the understanding of the evolutionary morphology of mammals.

zoology↗

bioRxiv2019

Paternal age affects offspring's behavior possibly via an epigenetic mechanism recruiting a transcriptional repressor REST

Advanced paternal age has deleterious effects on mental health of next generation. Using a mouse model, we have confirmed that offspring derived from aged fathers showed impairments in behavior and abnormalities in the brain structure and activity. Comprehensive target DNA methylome analyses revealed in aged sperm more hypo-methylated genomic regions, in which REST/NRSF binding motif was enriched. Gene set enrichment analyses also identified enrichment of "REST/NRSF target genes", in addition to "Late-fetal genes" and autism spectrum disorder-related "SFARI genes", in up-regulated genes of developing brains from aged father. Indeed, gene sets near hypo-methylated genomic regions with REST/NRSF binding motif were also enriched in up-regulated genes of developing brains. Taken altogether, DNA hypo-methylation due to paternal aging in sperm will induce leaky expression of REST/NRSF target genes in the developing brain, thereby causing neuronal abnormalities and subsequent behavioral alteration in offspring.

neuroscience↗