Biology subjects

Yamauchi, S.

Publications and source records attributed to Yamauchi, S..

8 recordsLinked to original sources

bioRxiv2026

3D, multi-omic imaging reveals molecular biomarkers of the pre-metastatic niche in lung cancer

The recurrence rate following complete surgical resection of primary non-small cell lung cancer is as high as 55%, yet no approach currently exists to evaluate the risk of local recurrence. The premetastatic paradigm is the recognition that metastasis is preceded by reprogramming naive tissues to prime a microenvironment for tumor cell survival and subsequent reactivation. Identification of biomarkers of the pre-metastatic niche would allow us to evaluate a patients risk of local relapse in the normal lung parenchyma surrounding the resected tumor. We designed a workflow incorporating in vivo modelling, radiology, and deep learning-guided three-dimensional (3D) imaging, spatial proteomics, and transcriptomics to identify previously unreported signals associated with the early transformation of the lung parenchyma announcing regional metastasis. We curated biorepository spanning timepoints before and after resection of primary Lewis Lung Carcinoma (LLC) tumors. Using radiology and cellular resolution 3D histology, we calculated the number and distribution of metastases in mouse lungs and developed an algorithm to guide placement of spatial proteomics and transcriptomics to regions containing early micro-metastases and the pre-metastatic microenvironment. Molecular and tissue features associated with presence, size, and location of metastases guided the identification of both myeloid (F4/80) and senescent (p16/p21) cell signatures in the premetastatic and metastatic environments. Finally, multiparametric flow cytometry of metastatic lungs in a senescence reporter GEMM (tdTomato-p16 INKA mice) resolved senescent cells including alveolar macrophages as the cellular phenotypes associated with these early premetastatic signatures. Altogether, this work highlights a novel AI-assisted approach for detection of biomarkers of tissue remodeling during lung cancer invasion.

bioengineering↗

bioRxiv2026

Embryonic and larval development of the Pacific saury Cololabis saira: Distinctive characteristics of a rapidly growing beloniform fish

BackgroundPacific saury Cololabis saira is one of the important food resources drawing attention for its recent rapid decline of catch. Their life cycle and embryonic development have been largely unknown. It is important to clarify how the habitat and reproduction of this species have been affected by the global changes of aquatic environment. ResultsWe obtained fertilized eggs of C. saira, by spontaneous spawning and artificial fertilization, and observed the embryonic development up to larval stages. Embryonic stages are documented with major periods of developmental events; cleavage, gastrulation (epiboly) and somitogenesis and organogenesis. Remarkably, segmentation of somites starts in the middle of epiboly, unlike other well-documented teleost species such as zebrafish and medaka. Morphological changes in larval stage up to feeding juvenile is also described. Growth speed of larval Pacific saury is dramatically rapid, in comparison to closely related beloniform fish such as medaka. ConclusionsIn comparison to medaka, early embryogenesis of saury proceeds slowly, although being followed by early onset of somitogenesis. This might be partly responsible for the rapid growth into adult (larger than 20 cm in body length) in only half a year. Further studies on embryonic development will uncover the molecular mechanisms underlying the characteristics of Pacific saury as an excellent source of nutrition and as an indicator of major environmental changes such as global warming.

developmental biology↗

bioRxiv2024

MAP4K1 and MAP4K2 regulate ABA-induced and Ca2+-mediated stomatal closure in Arabidopsis

Abscisic acid (ABA)-induced stomatal closure limits water loss from plants under drought stress. To investigate signaling pathways involved in stomatal closure, we performed a phosphoproteomic analysis of ABA-treated Arabidopsis guard cell protoplasts (GCPs). From this analysis, we discovered that MITOGEN-ACTIVATED PROTEIN 4 KINASE 1 (MAP4K1) is phosphorylated in response to ABA. Subsequent biochemical assays showed that Ser-479 of MAP4K1 is directly phosphorylated by SRK2E (OST1/SnRK2.6), a protein kinase that plays a central role in ABA-induced responses. Mutational analyses of MAP4K1, as well as closely related MAP4K2, revealed that both kinases positively regulate ABA-induced stomatal closure, and that Ser-479 of MAP4K1 was required for this phenotype. In map4k1map4k2, stomatal closure was induced by exogenous Ca2+ but not H2O2. Furthermore, electrophysiology experiments showed that MAP4K1/2 are required for ABA-dependent activation of Ca2+-permeable channels in GCPs. Together, our results indicate that SnRK2 and MAP4K1/2 function as a signaling module to regulate Ca2+-mediated stomatal closure.

plant biology↗

bioRxiv2023

Chromosomal DNA sequences of the Pacific saury genome: versatile resources for fishery science and comparative biology

Pacific saury (Cololabis saira) is a commercially important small pelagic fish species in Asian. In this study, we conducted the first-ever whole genome sequencing of this species, with single molecule, real-time (SMRT) sequencing technology. The obtained high-fidelity (HiFi) long-read sequence data, which amount to approximately 30 folds of its haploid genome size that was measured with quantitative PCR (1.17 Gb), were assembled into contigs. Scaffolding with Hi-C reads yielded a whole genome assembly containing 24 chromosome-scale sequences, with a scaffold N50 length of 47.7 Mb. Screening of repetitive elements including telomeric repeats was performed to characterize possible factors that need to be resolved towards telomere-to-telomere sequencing. The larger genome size than in medaka, a close relative in Beloniformes, is at least partly explained by larger repetitive element quantity, which is reflected in more abundant tRNAs, in the Pacific saury genome. Protein-coding regions was predicted using transcriptome data, which resulted in 22,274 components. Retrieval of Pacific saury homologs of aquaporin (AQP) genes known from other teleost fishes validated high completeness and continuity of the genome assembly. These resources are available at https://treethinkers.nig.ac.jp/saira/ and will assist various molecular-level studies in fishery science and comparative biology.

genomics↗

bioRxiv2023

ASK1 promotes inflammation in senescence and aging

Cellular senescence is a stress-induced, permanent cell cycle arrest involved in tumor suppression and aging. Senescent cells secrete bioactive molecules such as pro-inflammatory cytokines and chemokines. This senescence-associated secretory phenotype (SASP) has been implicated in immune-mediated elimination of senescent cells and age-associated chronic inflammation. However, the mechanisms regulating the SASP are incompletely understood. Here, we show that the stress-responsive kinase ASK1 promotes inflammation in senescence and aging. ASK1 is activated during senescence and increases the expression of pro-inflammatory cytokines and chemokines by activating p38, a kinase critical for the SASP. ASK1-deficient mice show impaired elimination of oncogene-induced senescent cells and an increased rate of tumorigenesis. Furthermore, ASK1 deficiency prevents age-associated p38 activation and inflammation and attenuates glomerulosclerosis. Our results suggest that ASK1 is a driver of the SASP and age-associated chronic inflammation and represents a potential therapeutic target for age-related diseases.

cell biology↗

bioRxiv2022

DNA damage response signaling to mitochondria drives senescence

Cellular senescence is a stress-induced irreversible cell cycle arrest typically accompanied by expression of the cyclin-dependent kinase inhibitor p16INK4a (hereafter referred to as p16) and mitochondrial dysfunction1. Recent studies have indicated that p16-expressing senescent cells accumulate in the body over time and contribute to aging1, 2. Many stresses, such as telomere shortening and oncogene activation, induce senescence by damaging nuclear DNA1. However, the molecular mechanisms linking DNA damage to senescence remain unclear. Here, we show that the outer mitochondrial transmembrane protein BNIP3 drives senescence by triggering a DNA damage response (DDR) of mitochondria. BNIP3 was identified in a genome-wide siRNA screen for genes required for p16 expression upon DNA damage. Mass spectrometric analysis of BNIP3-interacting proteins yielded the DDR kinase ATM and subunits of the mitochondrial contact site and cristae organizing system (MICOS) complex. BNIP3 is an ATM substrate that increases the number of mitochondrial cristae upon DNA damage. This increase enhances the oxidation of fatty acids to acetyl-CoA, an acetyl group donor, thereby promoting histone acetylation and associated p16 expression. Our findings indicate that DDR signaling to mitochondria promotes p16 expression by altering mitochondrial structure and metabolism and highlight the importance of nuclear-mitochondrial communication in senescence induction.

cell biology↗

bioRxiv2021

A unified framework for measuring selection on cellular lineages and traits

Intracellular states probed by gene expression profiles and metabolic activities are intrinsically noisy, causing phenotypic variations among cellular lineages. Understanding the adaptive and evolutionary roles of such variations requires clarifying their linkage to population growth rates. Extending a cell lineage statistics framework, here we show that a populations growth rate can be expanded by fitness cumulants of any cell lineage trait. The expansion enables quantifying the contribution of each fitness cumulant, such as variance and skewness, to population growth. We introduce a function that contains all the essential information of cell lineage statistics, including mean lineage fitness and selection strength. We reveal a relation between fitness heterogeneity and population growth rate response to perturbation. We apply the framework to experimental cell lineage data from bacteria to mammalian cells, revealing that third or higher-order cumulants contributions are negligible under constant growth conditions but could be significant in regrowing processes from growth-arrested conditions. Furthermore, we identify cellular populations in which selection leads to an increase of fitness variance among lineages. The framework assumes no particular growth models or environmental conditions, and is thus applicable to various biological phenomena for which phenotypic heterogeneity and cellular proliferation are important.

systems biology↗

bioRxiv2020

Hydroxyl carlactone derivatives are predominant strigolactones in Arabidopsis

Strigolactones (SLs) regulate important aspects of plant growth and stress responses. Many diverse types of SL occur in plants, but a complete picture of biosynthesis remains unclear. In Arabidopsis thaliana, we have demonstrated that MAX1, a cytochrome P450 monooxygenase, converts carlactone (CL) into carlactonoic acid (CLA), and that LBO, a 2-oxoglutarate-dependent dioxygenase, converts methyl carlactonoate (MeCLA) into a metabolite called [MeCLA+16] Da. In the present study, feeding experiments with deuterated MeCLAs revealed that [MeCLA+16] Da is hydroxymethyl carlactonoate (1-HO-MeCLA). Importantly, this LBO metabolite was detected in plants. Interestingly, other related compounds, methyl 4-hydroxycarlactonoate (4-HO-MeCLA) and methyl 16-hydroxycarlactonoate (16-HO-MeCLA) were also found to accumulate in lbo mutants. 3-HO-, 4-HO- and 16-HO-CL were detected in plants, but their expected corresponding metabolites, HO-CLAs, were absent in max1 mutants. These results suggest that HO-CL derivatives are predominant SLs in Arabidopsis, produced through MAX1 and LBO.

plant biology↗