Biology subjects

Hashidate-Yoshida, T.

Publications and source records attributed to Hashidate-Yoshida, T..

4 recordsLinked to original sources

bioRxiv2025

Molecular signature of COVID-19 prior to its exacerbation by multi-omics survey

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic due to its high transmissibility and ability to evade innate immune responses. Comprehensive characterization of the disease is essential for elucidating its pathophysiology and clinical progression. In this study, we performed multi-omics analyses of plasma samples collected from SARS-CoV-2-positive patients prior to clinical deterioration of coronavirus disease 2019 (COVID-19). These samples revealed the potential of previously reported clinical parameters, including CRP and neutrophil level, to predict COVID-19 exacerbation in the early stage. Our analysis identified a novel panel of molecules that precede the clinical manifestations associated with COVID-19 progression. These candidate biomarkers exhibited strong correlations with previously reported clinical and immunological parameters. Notably, several inflammation-related markers showed inverse associations with specific interferon subtypes, including IFN-6 and IFN-8, potentially reflecting mechanisms of SARS-CoV-2-mediated immune evasion. Our findings contribute to the understanding of virus-induced acute exacerbation and offer a valuable foundation for future pandemic research.

microbiology↗

bioRxiv2025

MBOAT2 limits the amounts of PUFA in phosphatidylcholine of neonatal and dystrophic skeletal muscle and promotes muscle regeneration

Skeletal muscle regeneration is critically shaped by lipid remodeling, yet regulatory mechanisms involved remain unexplored. We identify MBOAT2, a lysophospholipid acyltransferase highly induced in activated satellite cells, as a key enzyme that limits the amounts of polyunsaturated fatty acids (PUFAs) in phosphatidylcholine (PC). Lipidomic profiling reveals a characteristic PC signature--high in monounsaturated fatty acids (MUFAs) and low in PUFAs--in dystrophic, injured, and neonatal muscle, paralleling elevated Mboat2 expression. Given the susceptibility of PUFAs to oxidative damage and the emerging role of lipid peroxidation in driving muscle atrophy during denervation, disuse, and aging, MBOAT2-mediated enrichment of MUFA-PC may represent a protective and pro-regenerative lipid environment. Loss- and gain-of-function approaches confirm that MBOAT2 remodels PC and promotes myogenic repair. Our findings uncover a lipid remodeling circuit in muscle stem cells that buffers oxidative stress and highlight that MBOAT2 may improve regenerative capacity in muscular dystrophy, sarcopenia, and other muscle-wasting conditions. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/686003v1_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@e9acddorg.highwire.dtl.DTLVardef@1541b14org.highwire.dtl.DTLVardef@bdfe54org.highwire.dtl.DTLVardef@1844b89_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2020

Establishment of a highly efficient gene disruption strategy to analyze and manipulate lipid co-regulatory networks

Gene disruption has been dramatically facilitated by genome editing tools. Despite improvements in gene disruption rates in cultured cells, clone isolation remains routinely performed to obtain mutants, potentially leading to artifacts due to clonal variation in cellular phenotypes. Here we report GENF, a highly efficient strategy to disrupt genes without isolating clones, which can be multiplexed. Using it, we obtained reliable lipidomics datasets from mutant cells without being affected by variances related to clone isolation. Through this, we found that an enzyme involved in congenital generalized lipodystrophy regulates glycerophospholipids with specific acyl-chains. We also demonstrate the possibility to dissect complex lipid co-regulatory mechanisms, explaining cell adaptations to altered lipid metabolism. With its simplicity and the avoidance of cloning-related artifacts, GENF is likely to contribute to many cell biology studies, especially those involving -omics approaches.

genetics↗

bioRxiv2018

Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo

Hematopoietic stem cells (HSCs) maintain lifelong hematopoiesis by remaining quiescent in the bone marrow niche. Recapitulation of a quiescent state in culture has not been achieved, as cells rapidly proliferate and differentiate in vitro. After exhaustive analysis of different environmental factor combinations and concentrations as a way to mimic physiological conditions, we were able to maintain engraftable quiescent HSCs for 1 month in culture under very low cytokine concentrations, hypoxia, and very high fatty acid levels. Exogenous fatty acids were required likely due to suppression of intrinsic fatty acid synthesis by hypoxia and low cytokine conditions. By contrast, high cytokine concentrations or normoxia induced HSC proliferation and differentiation. Our novel culture system provides a means to evaluate properties of steady state HSCs and test effects of defined factors in vitro under near-physiological conditions.

cell biology↗