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Emergence of large-scale cell death through ferroptotic trigger waves

Nature 2024年第8021期631卷 654-662页

作者： Co, Hannah K. C. Wu, Chia-Chou Lee, Yi-Chen Chen, Sheng-Hong Molecular and Cell Biology Taiwan International Graduate Program Academia Sinica and Graduate Institute of Life Science National Defense Medical Center Laboratory for Cell Dynamics Institute of Molecular Biology Academia Sinica National Center for Theoretical Sciences Physics Division Genome and Systems Biology Degree Program Academia Sinica and National Taiwan University

Large-scale cell death is commonly observed during organismal development and in human pathologies1–5. These cell death events extend over great distances to eliminate large populations of cells, raising the question... 详细信息

Large-scale cell death is commonly observed during organismal development and in human pathologies^1–5. These cell death events extend over great distances to eliminate large populations of cells, raising the question of how cell death can be coordinated in space and time. One mechanism that enables long-range signal transmission is trigger waves⁶, but how this mechanism might be used for death events in cell populations remains unclear. Here we demonstrate that ferroptosis, an iron- and lipid-peroxidation-dependent form of cell death, can propagate across human cells over long distances (≥5 mm) at constant speeds (around 5.5 μm min⁻¹) through trigger waves of reactive oxygen species (ROS). Chemical and genetic perturbations indicate a primary role of ROS feedback loops (Fenton reaction, NADPH oxidase signalling and glutathione synthesis) in controlling the progression of ferroptotic trigger waves. We show that introducing ferroptotic stress through suppression of cystine uptake activates these ROS feedback loops, converting cellular redox systems from being monostable to being bistable and thereby priming cell populations to become bistable media over which ROS propagate. Furthermore, we demonstrate that ferroptosis and its propagation accompany the massive, yet spatially restricted, cell death events during muscle remodelling of the embryonic avian limb, substantiating its use as a tissue-sculpting strategy during embryogenesis. Our findings highlight the role of ferroptosis in coordinating global cell death events, providing a paradigm for investigating large-scale cell death in embryonic development and human pathologies. © The Author(s) 2024.

关键词： cell death Dynamical systems Emergence Multistability Regulatory networks

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Brassinosteroid biosynthesis and signaling:Conserved and diversified functions of core genes across multiple plant species

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Plant Communications 2024年第9期5卷 72-100页

作者： Brian Zebosi Erik Vollbrecht Norman B.Best Department of Genetics Development and Cell BiologyIowa State UniversityAmesIA 50011USA Interdepartmental Genetics and Genomics Graduate Program Iowa State UniversityAmesIA 50011USA USDA-ARS Plant Genetics Research UnitColumbiaMO 65201USA

Brassinosteroids(BRs)are important regulators that control myriad aspects of plant growth and development,including biotic and abiotic stress responses,such that modulating BR homeostasis and signaling presents abundant opportunities for plant breeding and crop *** and other proteins involved in the biosynthesis and signaling of BRs are well understood from molecular genetics and phenotypic analysis in Arabidopsis thaliana;however,knowledge of the molecular functions of these genes in other plant species,especially cereal crop plants,is *** this manuscript,we comprehensively review functional studies of BR genes in Arabidopsis,maize,rice,Setaria,Brachypodium,and soybean to identify conserved and diversified functions across plant species and to highlight cases for which additional research is in *** performed phylogenetic analysis of gene families involved in the biosynthesis and signaling of BRs and re-analyzed publicly available transcriptomic *** trees coupled with expression data provide a valuable guide to supplement future research on BRs in these important crop species,enabling researchers to identify gene-editing targets for BR-related functional studies.

关键词： brassinosteroids maize rice Setaria soybean Brachypodium Arabidopsis

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cellular and Transcriptional Heterogeneity in the Intrahepatic Biliary Epithelium

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Gastro Hep Advances 2023年第1期2卷 108-120页

作者： Hrncir, Hannah R. Gracz, Adam D. Division of Digestive Diseases Department of Medicine Emory University Atlanta GA United States Graduate Program in Biochemistry Cell and Developmental Biology Emory University Atlanta GA United States Graduate Program in Genetics and Molecular Biology Emory University Atlanta GA United States

Epithelial tissues comprise heterogeneous cellular subpopulations, which often compartmentalize specialized functions such as absorption and secretion to distinct cell types. In the liver, hepatocytes and biliary epithelial cells (BECs;also called cholangiocytes) are the 2 major epithelial lineages and play distinct roles in (1) metabolism, protein synthesis, detoxification;and (2) bile transport and modification, respectively. Recent technological advances, including single-cell transcriptomic assays, have shed new light on well-established heterogeneity among hepatocytes, endothelial cells, and immune cells in the liver. However, a “ground truth” understanding of molecular heterogeneity in BECs has remained elusive, and the field currently lacks a set of consensus biomarkers for identifying BEC subpopulations. Here, we review long-standing definitions of BEC heterogeneity as well as emerging studies that aim to characterize BEC subpopulations using next-generation single-cell assays. Understanding cellular heterogeneity in the intrahepatic bile ducts holds promise for expanding our foundational mechanistic knowledge of BECs during homeostasis and disease. © 2023 The Authors

关键词： cellular heterogeneity Cholangiocyte Intrahepatic bile ducts Liver Single cell biology

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Brain age estimation:premise,promise,and problems

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Neural Regeneration Research 2025年第8期20卷 2313-2314页

作者： Jarrad Perron Ji Hyun Ko Graduate Program in Biomedical Engineering Price Faculty of EngineeringUniversity of ManitobaWinnipegMBCanada PrairieNeuro Research Centre Kleysen Institute for Advanced MedicineHealth Sciences CentreWinnipegMBCanada Department of Human Anatomy and Cell Science Rady Faculty of Health SciencesUniversity of ManitobaWinnipegMBCanada

Premise:The com bined effects of modern healthcare practices which prolong lifespan and declining birthrates have created unprecedented changes in age demographics worldwide that are especially pronounced in Japan,South Korea,Europe,and North *** old age is the most significant predictor of dementia,global healthcare systems must rise to the challenge of providing care for those with neurodegenerative disorders.

关键词： estimation providing birth

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Cyto and genotoxicity induced by acute exposure to Novacron® Bold Deep Navy dye on Astyanax lacustris can be reduced after treatment through a vertical flow constructed wetland system

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Environmental Science and Pollution Research 2024年第59期31卷 66630-66642页

作者： da Silva, Josiane Rodrigues Rocha de Andrade, Camila Oliveira Ribeiro, Anna Carla Macruz, Paula Derksen Bergamasco, Rosângela Fernandes, Carlos Alexandre Graduate Program of Environmental Biotechnology Department of Biotechnology Genetics and Cell Biology State University of Maringá Paraná Maringá Brazil Department of Chemistry State University of Maringá Paraná Maringá Brazil Department of Chemical Engineering State University of Maringá Paraná Maringá Brazil Biological Sciences Center State University of Maringá Paraná Maringá Brazil Department of Biotechnology Genetics and Cell Biology State University of Maringá Avenida Colombo 5790 Paraná MaringáCEP 87020-900 Brazil

Reactive dyes used in the textile industry can be harmful to aquatic organisms. This study aimed to evaluate the potential cyto/genotoxic effects of the Novacron® Bold Deep Navy reactive dye on fish Astyanax lacustris before and after treatment through a vertical flow constructed wetland system (VFCW). Micronucleus test (MN), cellular morphological changes (CMC), and the comet assay were used to assess the effects of the dye in erythrocytes. During the experiment, A. lacustris specimens were exposed to sublethal concentrations (10, 20, 30, and 40 mg/L) of Novacron® Bold Deep Navy dye for 96 h. Results showed that the dye caused MN formation (27), DNA damage, and several types of CMC (3513) in all tested concentrations on A. lacustris. Notably, analyses were significant (p © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.

关键词： Textile industry

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Harnessing novel engineered feeder cells expressing activating molecules for optimal expansion of NK cells with potent antitumor activity

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cellular & Molecular Immunology 2022年第2期19卷 296-298页

作者： Bokyung Min Bitna Yang You-Sun Kim Gyeong Min Park HyunAh Kim Hyojin Kim Eun-Ji Kim Yu Kyeong Hwang Eui-Cheol Shin Sungyoo Cho BioMedical Science and Engineering Interdisciplinary Program KAISTDaejeonKorea Cell Therapy Research Center GC LabCellYonginKorea Laboratory of Immunology and Infectious Diseases Graduate School of Medical Science and EngineeringKAISTDaejeonKorea

Natural killer(NK)cells play an important role in the antitumor immune response as the major cytotoxic lymphocytes in the innate immune *** cells without any genetic modifications have been used for both autologous and allogeneic ***,many reports have suggested that allogeneic NK cells can reduce the recurrence of disease and improve survival through a graft-versus-leukemia effect without GVHD[1,2].

关键词： killer expressing optimal

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Characterization of a new triaxial nanofiber membrane and osteogenic differentiation capacity of human bone marrow mesenchymal stem cells for bone repair

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Journal of Materials Research 2025年 1-18页

作者： Altundag-Erdogan, Özlem Çetinkaya, Hayrullah Çelebi-Saltik, Betül Altun, Belgin Şahin, Mehtap Mağden, Gamze Kara Öteyaka, Mustafa Özgür Department of Stem Cell Sciences Graduate School of Health Sciences and Center for Stem Cell Research and Development Hacettepe University Sihhiye Ankara06100 Turkey Department of Chemical Engineering Eskisehir Osmangazi University Eskişehir26040 Turkey Vocational School Health Services Hacettepe University Sihhiye Ankara06100 Turkey BUGAMED Biotechnology Industry and Trade Inc Eskişehir26380 Turkey Eskişehir Vocational School Electronics and Automation Eskisehir Osmangazi University Mechatronic Program Eskişehir26250 Turkey

A triaxial nanofiber membrane was developed using a custom triaxial nozzle during electrospinning. The membrane consisted of three layers (outer middle (PVA-Collagen Type I-BMP-2), and inner (PVA-nHAP)). TEM revealed the diameters of the outer, middle, and inner layers as 167.5, 142.6, and 119.3 nm, respectively. The triaxial nanofiber membrane exhibited superior tensile strength (36 MPa) and elastic modulus (2.5 GPa), along with a roughness of 359 nm and hydrophilic properties. In addition, it demonstrated a 200% swelling ratio and reduced bacterial colonization by 10.8-fold. Both Calcium deposition and ALP activity were significantly higher and increased expression of BSP (eightfold), OCN (13-fold), and OPN (488-fold) genes were observed in membrane + OST groups (p © The Author(s), under exclusive licence to The Materials Research Society 2025.

关键词： Bone

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A newly evolved rice-specific gene JAUP1 regulates jasmonate biosynthesis and signalling to promote root development and multi-stress tolerance

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Plant Biotechnology Journal 2024年第5期22卷 1417-1432页

作者： Muzaffar, Adnan Chen, Yi-Shih Lee, Hsiang-Ting Wu, Cheng-Chieh Le, Trang Thi Liang, Jin-Zhang Lu, Chun-Hsien Balasubramaniam, Hariharan Lo, Shuen-Fang Yu, Lin-Chih Chan, Chien-Hao Chen, Ku-Ting Lee, Miin-Huey Hsing, Yue-Ie Ho, Tuan-Hua David Yu, Su-May Molecular and Cell Biology Taiwan International Graduate Program Academia Sinica Taipei Taiwan Graduate Institute of Life Sciences National Defense Medical Center Taipei Taiwan Institute of Molecular Biology Academia Sinica Taipei Taiwan Advanced Plant Biotechnology Center National Chung Hsing University Taichung Taiwan Institute of Plant and Microbial Biology Academia Sinica Taipei Taiwan Department of Agricultural Chemistry National Taiwan University Taipei Taiwan Genome and Systems Biology Degree Program National Taiwan University and Academia Sinica Taipei Taiwan Molecular and Biological Agricultural Sciences Taiwan International Graduate Program Academia Sinica and National Chung Hsing University Taipei Taiwan International Bachelor Program of Agribusiness National Chung Hsing University Taichung Taiwan Department of Plant Pathology National Chung Hsing University Taichung Taiwan

Root architecture and function are critical for plants to secure water and nutrient supply from the soil, but environmental stresses alter root development. The phytohormone jasmonic acid (JA) regulates plant growth and responses to wounding and other stresses, but its role in root development for adaptation to environmental challenges had not been well investigated. We discovered a novel JA Upregulated Protein 1 gene (JAUP1) that has recently evolved in rice and is specific to modern rice accessions. JAUP1 regulates a self-perpetuating feed-forward loop to activate the expression of genes involved in JA biosynthesis and signalling that confers tolerance to abiotic stresses and regulates auxin-dependent root development. Ectopic expression of JAUP1 alleviates abscisic acid- and salt-mediated suppression of lateral root (LR) growth. JAUP1 is primarily expressed in the root cap and epidermal cells (EPCs) that protect the meristematic stem cells and emerging LRs. Wound-activated JA/JAUP1 signalling promotes crosstalk between the root cap of LR and parental root EPCs, as well as induces cell wall remodelling in EPCs overlaying the emerging LR, thereby facilitating LR emergence even under ABA-suppressive conditions. Elevated expression of JAUP1 in transgenic rice or natural rice accessions enhances abiotic stress tolerance and reduces grain yield loss under a limited water supply. We reveal a hitherto unappreciated role for wound-induced JA in LR development under abiotic stress and suggest that JAUP1 can be used in biotechnology and as a molecular marker for breeding rice adapted to extreme environmental challenges and for the conservation of water resources. © 2024 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

关键词： ABA abiotic stress grain yield jasmonate rice root development

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Orphan nuclear receptors-induced ALT-associated PML bodies are targets for ALT inhibition

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Nucleic Acids Research 2024年第11期52卷 6472-6489页

作者： Marie Gaela, Venus Hsia, Hsuan-Yu Joseph, Nithila A. Tzeng, Wan-Yi Ting, Pin-Chao Shen, Yi-Ling Tsai, Chia-Tsen Boudier, Thomas Chen, Liuh-Yow Molecular and Cell Biology Taiwan International Graduate Program Academia Sinica Graduate Institute of Life Sciences National Defense Medical Center Taipei 11529 Taiwan Institute of Molecular Biology Academia Sinica Taipei 11529 Taiwan Insitute of Molecular and Cellular Biology National Taiwan University Taipei 106319 Taiwan Department and Graduate Institute of Microbiology and Immunology National Defense Medical Center Taipei 11490 Taiwan CENTURI multi-engineering platform Aix-Marseille Université Marseille 13288 France

Orphan nuclear receptors (NRs), such as COUP-TF1, COUP-TF2, EAR2, TR2 and TR4, are implicated in telomerase-negative cancers that maintain their telomeres through the alternative lengthening of telomeres (ALT) mechanism. However, how telomere association of orphan NRs is involved in ALT activation remains unclear. Here, we demonstrate that telomeric tethering of orphan NRs in human fibroblasts initiates formation of ALT-associated PML bodies (APBs) and features of ALT activity, including ALT telomere DNA synthesis, telomere sister chromatid exchange, and telomeric C-circle generation, suggesting de novo ALT induction. Overexpression of orphan NRs exacerbates ALT phenotypes in ALT cells, while their depletion limits ALT. Orphan NRs initiate ALT via the zinc finger protein 827, suggesting the involvement of chromatin structure alterations for ALT activation. Furthermore, we found that orphan NRs and deficiency of the ALT suppressor ATRX-DAXX complex operate in concert to promote ALT activation. Moreover, PML depletion by gene knockout or arsenic trioxide treatment inhibited ALT induction in fibroblasts and ALT cancer cells, suggesting that APB formation underlies the orphan NR-induced ALT activation. Importantly, arsenic trioxide administration abolished APB formation and features of ALT activity in ALT cancer cell line-derived mouse xenografts, suggesting its potential for further therapeutic development to treat ALT cancers. © The Author(s) 2024.

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A carnivorous mushroom paralyzes and kills nematodes via a volatile ketone

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Science Advances 2023年第3期9卷 000-000页

作者： Lee, Ching-Han Lee, Yi-Yun Chang, Yu-Chu Pon, Wen-Li Lee, Sue-Ping Wali, Niaz Nakazawa, Takehito Honda, Yoichi Shie, Jiun-Jie Hsueh, Yen-Ping Institute of Molecular Biology Academia Sinica Taipei11529 Taiwan Molecular Cell Biology Taiwan International Graduate Program Academia Sinica Graduate Institute of Life Science National Defense Medical Center Taipei Taiwan Department of Biochemistry and Molecular Cell Biology School of Medicine Taipei Medical University Taipei11031 Taiwan Institute of Chemistry Academia Sinica Taipei11529 Taiwan Institute of Biochemical Sciences National Taiwan University Taipei10617 Taiwan Chemical Biology and Molecular Biophysics Taiwan International Graduate Program Academia Sinica Taipei10617 Taiwan Graduate School of Agriculture Kyoto University Sakyo-ku Kyoto606-8502 Japan Department of Biochemical Science and Technology National Taiwan University Taipei10617 Taiwan Institute of Biochemistry and Molecular Biology College of Medicine National Taiwan University Taipei10051 Taiwan Department of Biochemical Science and Technology National Chiayi University Chiayi City60004 Taiwan

The carnivorous mushroom Pleurotus ostreatus uses an unknown toxin to rapidly paralyze and kill nematode prey upon contact. We report that small lollipop-shaped structures (toxocysts) on fungal hyphae are nematicidal and that a volatile ketone, 3-octanone, is detected in these fragile toxocysts. Treatment of Caenorhabditis elegans with 3-octanone recapitulates the rapid paralysis, calcium influx, and neuronal cell death arising from fungal contact. Moreover, 3-octanone disrupts cell membrane integrity, resulting in extracellular calcium influx into cytosol and mitochondria, propagating cell death throughout the entire organism. Last, we demonstrate that structurally related compounds are also biotoxic to C. elegans, with the length of the ketone carbon chain being crucial. Our work reveals that the oyster mushroom has evolved a specialized structure containing a volatile ketone to disrupt the cell membrane integrity of its prey, leading to rapid cell and organismal death in nematodes. Copyright © 2023 The Authors, some rights reserved

关键词： Ketones

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