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Single-cell transcriptomics uncovers EGFR signaling-mediated gastric progenitor cell differentiation in stomach homeostasis (vol 14, 3750, 2023)

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NATURE COMMUNICATIONS 2023年第1期14卷 1-16页

作者： Takada, Hitomi Sasagawa, Yohei Yoshimura, Mika Tanaka, Kaori Iwayama, Yoshimi Hayashi, Tetsutaro Isomura-Matoba, Ayako Nikaido, Itoshi Kurisaki, Akira Laboratory of Stem Cell Technologies Graduate School of Science and Technology Nara Institute of Science and Technology Takayama-cho Ikoma Nara Japan Laboratory for Bioinformatics Research RIKEN Center for Biosystems Dynamics Research Wako Saitama Japan Department of Functional Genome Informatics Biological Data Science Medical Research Institute Tokyo Medical and Dental University Bunkyo Tokyo Japan Master’s/Doctoral Program in Life Science Innovation (Bioinformatics) Degree Programs in Systems and Information Engineering Graduate School of Science and Technology University of Tsukuba Tsukuba Ibaraki Japan

Defects in gastric progenitor cell differentiation are associated with various gastric disorders, including atrophic gastritis, intestinal metaplasia, and gastric cancer. However, the mechanisms underlying the multilineage differentiation of gastric progenitor cells during healthy homeostasis remain poorly understood. Here, using a single-cell RNA sequencing method, Quartz-Seq2, we analyzed the gene expression dynamics of progenitor cell differentiation toward pit cell, neck cell, and parietal cell lineages in healthy adult mouse corpus tissues. Enrichment analysis of pseudotime-dependent genes and a gastric organoid assay revealed that EGFR-ERK signaling promotes pit cell differentiation, whereas NF-κB signaling maintains gastric progenitor cells in an undifferentiated state. In addition, pharmacological inhibition of EGFR in vivo resulted in a decreased number of pit cells. Although activation of EGFR signaling in gastric progenitor cells has been suggested as one of the major inducers of gastric cancers, our findings unexpectedly identified that EGFR signaling exerts a differentiation-promoting function, not a mitogenic function, in normal gastric homeostasis.

关键词： Adult stem cells Stem-cell differentiation Stem-cell niche

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One-step flow synthesis of size-controlled polymer nanogels in a fluorocarbon microfluidic chip

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RSC Advances 2024年第16期14卷 11258-11265页

作者： Montalbo, Reynaldo Carlos K. Wu, Meng-Jie Tu, Hsiung-Lin Institute of Chemistry Academia Sinica Taipei11529 Taiwan Nanoscience and Technology Taiwan International Graduate Program Academia Sinica Taipei11529 Taiwan Department of Engineering and System Science National Tsing-Hua University Hsinchu300044 Taiwan Department of Chemistry National Cheng-Kung University Tainan70101 Taiwan Genome and Systems Biology Degree Program Academia Sinica and National Taiwan University Taiwan

Synthetic polymer nanoparticles (NPs) with biomimetic properties are ideally suited for different biomedical applications such as drug delivery and direct therapy. However, bulk synthetic approaches can suffer from poor reproducibility and scalability when precise size control or multi-step procedures are required. Herein, we report an integrated microfluidic chip for the synthesis of polymer NPs. The chip could sequentially perform homopolymer synthesis and subsequent crosslinking into NPs without intermediate purification. This was made possible by fabrication of the chip with a fluorinated elastomer and incorporation of two microfluidic mixers. The first was a long channel with passive mixing features for the aqueous RAFT synthesis of stimuli-responsive polymers in ambient conditions. The polymers were then directly fed into a hydrodynamic flow focusing (HFF) junction that rapidly mixed them with a crosslinker solution to produce NPs. Compared to microfluidic systems made of PDMS or glass, our chip had better compatibility and facile fabrication. The polymers were synthesized with high monomer conversion and the NP size was found to be influenced by the flow rate ratio between the crosslinker solution and polymer solution. This allowed for the size to be predictably controlled by careful adjustment of the fluid flow rates. The size of the NPs and their stimuli-responses were studied using DLS and SEM imaging. This microfluidic chip design can potentially streamline and provide some automation for the bottom-up synthesis of polymer NPs while offering on-demand size control. © 2024 The Royal Society of Chemistry.

关键词： Microfluidic chips

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Chromatograms and Mass Spectra of High-Mannose and Paucimannose N-Glycans for Rapid Isomeric Identifications

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Journal of Proteome Research 2024年第3期23卷 939-955页

作者： Liew, Chia Yen Chen, Jien-Lian Lin, Yen-Ting Luo, Hong-Sheng Hung, An-Ti Magoling, Bryan John Abel Nguan, Hock-Seng Lai, Charles Pin-Kuang Ni, Chi-Kung Institute of Atomic and Molecular Sciences Academia Sinica Taipei 106216 Taiwan International Graduate Program of Molecular Science and Technology National Taiwan University Taipei 106216 Taiwan Molecular Science and Technology Taiwan International Graduate Program Academia Sinica Taipei 106216 Taiwan Department of Chemistry National Taiwan Normal University Taipei 116059 Taiwan Department of Chemistry National Tsing Hua University Hsinchu 300044 Taiwan Institute of Biochemical Sciences College of Life Science National Taiwan University Taipei 106216 Taiwan Chemical Biology and Molecular Biophysics Program Taiwan International Graduate Program Academia Sinica Taipei 115201 Taiwan Genome and Systems Biology Degree Program National Taiwan University and Academia Sinica Taipei 106216 Taiwan

N-Linked glycosylation is one of the most essential post-translational modifications of proteins. However, N-glycan structural determination remains challenging because of the small differences in structures between isomers. In this study, we constructed a database containing collision-induced dissociation MSⁿ mass spectra and chromatograms of high-performance liquid chromatography for the rapid identification of high-mannose and paucimannose N-glycan isomers. These N-glycans include isomers by breaking of arbitrary numbers of glycosidic bonds at arbitrary positions of canonical Man₉GlcNAc₂ N-glycans. In addition, some GlcMan_nGlcNAc₂ N-glycan isomers were included in the database. This database is particularly useful for the identification of the N-glycans not in conventional N-glycan standards. This study demonstrated the application of the database to structural assignment for high-mannose N-glycans extracted from bovine whey proteins, soybean proteins, human mammary epithelial cells, and human breast carcinoma cells. We found many N-glycans that are not expected to be generated by conventional biosynthetic pathways of multicellular eukaryotes. © 2024 The Authors. Published by American Chemical Society.

关键词： bovine whey protein chromatogram CID spectra high-mannose N-glycans human breast carcinoma cell human mammary epithelial cell LODES/MSn logically derived sequence tandem mass spectrometry soybean protein structure

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Folding angle and wing flexibility influence the flight performance of origami winged fruits

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Nonlinear Dynamics 2024年第13期112卷 10995-11011页

作者： Cai, Jing-Fang Hsu, Ya-Chun Yen, Yu-Chen Lee, Yun-Chung Peyton, Bernie Huang, Mei-Jiau Yu, Hon-Tsen Juang, Jia-Yang Department of Mechanical Engineering National Taiwan University Taipei106319 Taiwan Department of Life Science National Taiwan University Taipei106319 Taiwan Berkeley CA United States Program in Nanoengineering and Nanoscience Graduate School of Advanced Technology National Taiwan University Taipei106319 Taiwan Degree Program of Genome and Systems Biology National Taiwan University Taipei106319 Taiwan

Winged fruits possess a unique flight mechanism relying on simple geometric structures rather than neuromuscular control. This study proposes an innovative approach using origami techniques to create three-winged model fruits, serving as a proxy for understanding the flight dynamics of natural winged fruits. Paper is employed to simulate inherent wing flexibility, with the option to add plastic frames for rigidity. We comprehensively investigate the free fall motion of both rigid and flexible winged fruits through experimental and numerical analyses. Velocity–time curves reveal a three-stage descent pattern—acceleration, deceleration, and steady states. The overshoot phenomenon is attributed to rapid lift increase due to leading-edge vortices attaching stably to the wings. This insight sheds light on aerodynamics governing fruit flight. Compared with rigid wings, flexible wings exhibit two key properties—slower descent and higher self-orienting capability—that facilitate a more stable and longer-distance dispersal of seeds under crosswind conditions. Our study demonstrates the potential benefits of flexible wings in natural seed distribution. This study advances our understanding of winged fruit flight dynamics, utilizing origami as a powerful tool for biomimetic investigations. The findings have broad implications, from improving aerodynamic designs to developing efficient micro air vehicles and electronic microfliers, and understanding seed dispersal evolution. Graphical abstract: (Figure presented.). © The Author(s), under exclusive licence to Springer Nature B.V. 2024.

关键词： Fruits

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Lin28a maintains a subset of adult muscle stem cells in an embryonic-like state

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细胞研究（英文版） 2023年第9期33卷 712-726页

作者： Peng Wang Xupeng Liu Ziyue Yao Yu Chen Lanfang Luo Kun Liang Jun-Hao Elwin Tan Min-Wen Jason Chua Yan-Jiang Benjamin Chua Shilin Ma Liping Zhang Wenwu Ma Shuqing Liu Wenhua Cao Luyao Guo Lu Guang Yuefan Wang He Zhao Na Ai Yun Li Chunwei Li Ruiqi Rachel Wang Bin Tean Teh Lan Jiang Kang Yu Ng Shyh Chang Institute of Zoology Chinese Academy of SciencesBeijingChina Beijing.Institute for Stem Cell and Regenerative Medicine Institute for Stem Cell and RegenerationChinese Academy of SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina NUS Graduate School for Integrative Sciences and Engineering National University of SingaporeSingaporeSIngapore institute of Molecular and Cell Biology Genome Institute of SingaporeAgency for Science Technology and ResearchSingaporeSingapore Laboratory of Cancer Therapeutics Program in Cancer and Stem Cell BiologyDuke-National University of Singapore Medical SchoolSingaporeSingapore Laboratory of Cancer Epigenome Division of Medical ScienceNational Cancer Centre SingaporeSingaporeSingapore University of Chinese Academy of Sciences BeijingChina CAS Key Laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijingChina Department of Clinical Nutrition Peking Union Medical College HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina Institute of Zoology Chinese Academy of SciencesBeijingChina Beijing.Institute for Stem Cell and Regenerative Medicine Institute for Stem Cell and RegenerationChinese Academy of SciencesBeijingChina Laboratory of Cancer Therapeutics Program in Cancer and Stem Cell BiologyDuke-National University of Singapore Medical SchoolSingaporeSingapore Laboratory of Cancer Epigenome Division of Medical ScienceNational Cancer Centre SingaporeSingaporeSingapore CAS Key Laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijingChina

During homeostasis and after injury,adult muscle stem cells(MuSCs)activate to mediate muscle ***,much remains unclear regarding the heterogeneous capacity of MuSCs for self-renewal and ***,we show that Lin28a is expressed in embryonic limb bud muscle progenitors,and that a rare reserve subset of Lin28a+Pax7-skeletal MuSCs can respond to injury at adult stage by replenishing the Pax7+MuSC pool to drive muscle *** with adult Pax7+MuSCs,Lin28a+MuSCs displayed enhanced myogenic potency in vitro and in vivo upon *** epigenome of adult Lin28a+MuSCs showed resemblance to embryonic muscle *** addition,RNA-sequencing revealed that Lin28a+MuSCs co-expressed higher levels of certain embryonic limb bud transcription factors,telomerase components and the p53 inhibitor Mdm4,and lower levels of myogenic differentiation markers compared to adult Pax7+MuSCs,resulting in enhanced self-renewal and stress-response ***,conditional ablation and induction of Lin28a+MuSCs in adult mice revealed that these cells are necessary and sufficient for efficient muscle ***,our findings connect the embryonic factor Lin28a to adult stem cell self-renewal and juvenile regeneration.

关键词： Muscle stem cells Regeneration

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Micropatterning of functional lipid bilayer assays for quantitative bioanalysis

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Biomicrofluidics 2023年第3期17卷 031302页

作者： Montalbo, Reynaldo Carlos K. Tu, Hsiung-Lin Institute of Chemistry Academia Sinica Taipei11529 Taiwan Nanoscience and Technology Taiwan International Graduate Program Academia Sinica Taipei11529 Taiwan Department of Engineering and System Science National Tsing-Hua University Hsinchu300044 Taiwan Genome and Systems Biology Degree Program Academia Sinica National Taiwan University Taipei10617 Taiwan

Interactions of the cell with its environment are mediated by the cell membrane and membrane-localized molecules. Supported lipid bilayers have enabled the recapitulation of the basic properties of cell membranes and have been broadly used to further our understanding of cellular behavior. Coupled with micropatterning techniques, lipid bilayer platforms have allowed for high throughput assays capable of performing quantitative analysis at a high spatiotemporal resolution. Here, an overview of the current methods of the lipid membrane patterning is presented. The fabrication and pattern characteristics are briefly described to present an idea of the quality and notable features of the methods, their utilizations for quantitative bioanalysis, as well as to highlight possible directions for the advanced micropatterning lipid membrane assays. © 2023 Author(s).

关键词： Lipid bilayers

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An integrated genetic-epigenetic analysis shed light on the mechanisms linking coronavirus disease 2019 (COVID-19) and cancer

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Cancer Communications 2021年第4期41卷 349-353页

作者： Zheng Dong Huiguang Yi Centre for Molecular Medicine and Therapeutics British Columbia Children’s Hospital Research InstituteUniversity of British ColumbiaVancouverBritish Columbia V5Z 4H4Canada Genome Science and Technology Graduate Program University of British ColumbiaVancouverBritish Columbia V5Z 4S6Canada Department of Epidemiology and Biostatistics University of GeorgiaAthensGeorgia 30602USA

Dear editor,The Coronavirus disease 2019(COVID-19)is an emerging disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection[1,2].It has spread rapidly across the world and caused a global health *** of 10 February 2021,COVID-19 has caused 2,333,446 deaths *** majority of COVID-19 deaths had comorbidities including cancer[1,2].

关键词： cancer acute respiratory

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Biomedical data and AI

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science China Life sciences 2025年第5期68卷 1536-1540页

作者： Hao Xu Shibo Zhou Zefeng Zhu Vincenzo Vitelli Liangyi Chen Ziwei Dai Ning Yang Luhua Lai Shengyong Yang Sergey Ovchinnikov Zhuoran Qiao Sirui Liu Chen Song Jianfeng Pei Han Wen Jianfeng Feng Yaoyao Zhang Zhengwei Xie Yang-Yu Liu Zhiyuan Li Fulai Jin Hao Li Mohammad Lotfollahi Xuegong Zhang Ge Yang Shihua Zhang Ge Gao Pulin Li Qi Liu Jing-Dong Jackie Han Peking-Tsinghua Center for Life Sciences (CLS) Academy for Advanced Interdisciplinary StudiesPeking University Center for Quantitative Biology (CQB) Academy for Advanced Interdisciplinary StudiesPeking University Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program Academy for Advanced Interdisciplinary StudiesPeking University Department of Physics University of Chicago School of Life Sciences Southern University of Science and Technology Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies College of Chemistry and Molecular Engineering Peking University Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan University Department of Biology Massachusetts Institute of Technology Lambic Therapeutics Inc. Changping Laboratory Al for Science Institute Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence Fudan University Department of Obstetrics and Gynecology West China Second University HospitalSichuan University Peking University International Cancer Institute and Peking University-Yunnan Baiyao International Medical Institute and State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular PharmacologySchool of Pharmaceutical SciencesPeking University Health Science CenterPeking University Channing Division of Network Medicine Department of MedicineBrigham and Women's Hospital and Harvard Medical School Center for Artificial Intelligence and Modeling the Carl R.Woese Institute for Genomic BiologyUniversity of Illinois Urbana-Champaign Department of Genetics and Genome Sciences School of Medicine and Department of Computer and Data Sciences and Department of Population and Quantitative Health SciencesCase Western Reserve University Department of Biochemistry and Biophysics University of California Sanger Institute Department of Automation Tsinghua University State Key Laboratory of Multimodal Artificial Intelligence Systems I

The development of artificial intelligence(AI) and the mining of biomedical data complement each other. From the direct use of computer vision results to analyze medical images for disease screening, to now integrating biological knowledge into models and even accelerating the development of new AI based on biological discoveries, the boundaries of both are constantly expanding, and their connections are becoming closer.

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Quantum simulation of an extended Dicke model with a magnetic solid

Communications Materials

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Communications Materials 2024年第1期5卷 42页

作者： Marquez Peraca, Nicolas Li, Xinwei Moya, Jaime M. Hayashida, Kenji Kim, Dasom Ma, Xiaoxuan Neubauer, Kelly J. Fallas Padilla, Diego Huang, Chien-Lung Dai, Pengcheng Nevidomskyy, Andriy H. Pu, Han Morosan, Emilia Cao, Shixun Bamba, Motoaki Kono, Junichiro Department of Physics and Astronomy Rice University HoustonTX United States Department of Physics California Institute of Technology PasadenaCA United States Applied Physics Graduate Program Smalley–Curl Institute Rice University HoustonTX United States Division of Applied Physics Graduate School of Engineering Hokkaido University Hokkaido Japan Department of Electrical and Computer Engineering Rice University HoustonTX United States Department of Physics International Center of Quantum and Molecular Structures and Materials Genome Institute Shanghai University Shanghai China Department of Physics and Center for Quantum Frontiers of Research and Technology National Cheng Kung University Tainan Taiwan Department of Chemistry Rice University HoustonTX United States Department of Physics I Kyoto University Kyoto Japan The Hakubi Center for Advanced Research Kyoto University Kyoto Japan PRESTO Japan Science and Technology Agency Saitama Japan Department of Physics Yokohama National University Yokohama Japan Department of Materials Science and NanoEngineering Rice University HoustonTX United States

The Dicke model describes the cooperative interaction of an ensemble of two-level atoms with a single-mode photonic field and exhibits a quantum phase transition as a function of light–matter coupling strength. Extending this model by incorporating short-range atom–atom interactions makes the problem intractable but is expected to produce new physical phenomena and phases. Here, we simulate such an extended Dicke model using a crystal of ErFeO3, where the role of atoms (photons) is played by Er3+ spins (Fe3+ magnons). Through terahertz spectroscopy and magnetocaloric effect measurements as a function of temperature and magnetic field, we demonstrated the existence of a novel atomically ordered phase in addition to the superradiant and normal phases that are expected from the standard Dicke model. Further, we elucidated the nature of the phase boundaries in the temperature–magnetic-field phase diagram, identifying both first-order and second-order phase transitions. These results lay the foundation for studying multiatomic quantum optics models using well-characterized many-body solid-state systems. © The Author(s) 2024.

关键词： Atoms

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Α γ-tubulin complex-dependent pathway suppresses ciliogenesis by promoting cilia disassembly

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Cell Reports 2022年第7期41卷 000-000页

作者： Shankar, Sahana Hsu, Zi-Ting Ezquerra, Artur Li, Chien-Chien Huang, Tzu-Lun Coyaud, Etienne Viais, Ricardo Grauffel, Cédric Raught, Brian Lim, Carmay Lüders, Jens Tsai, Su-Yi Hsia, Kuo-Chiang Molecular and Cell Biology Taiwan International Graduate Program Academia Sinica and National Defense Medical Center Taipei 11490 Taiwan Institute of Molecular Biology Academia Sinica Taipei 11529 Taiwan Department of Life Science National Taiwan University Taipei 10617 Taiwan Institute for Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology Barcelona 08028 Spain Princess Margaret Cancer Centre University Health Network 101 College Street Toronto M5G 1L7 ON Canada Department of Medical Biophysics University of Toronto Toronto M5G 1L7 ON Canada Institute of Biomedical Sciences Academia Sinica Taipei Taiwan Research Center for Developmental Biology and Regenerative Medicine National Taiwan University Taipei 10617 Taiwan Genome and Systems Biology Degree Program National Taiwan University and Academia Sinica Taipei 10617 Taiwan Institute of Biochemistry and Molecular Biology College of Life Sciences National Yang-Ming University Taipei 11221 Taiwan

The primary cilium, a microtubule-based sensory organelle, undergoes cycles of assembly and disassembly that govern the cell cycle progression critical to cell proliferation and differentiation. Although cilia assembly has been studied extensively, the molecular mechanisms underlying cilia disassembly are less well understood. Here, we uncover a γ-tubulin ring complex (γ-TuRC)-dependent pathway that promotes cilia disassembly and thereby prevents cilia formation. We further demonstrate that Kif2A, a kinesin motor that bears microtubule-depolymerizing activity, is recruited to the cilium basal body in a γ-TuRC-dependent manner. Our mechanistic analyses show that γ-TuRC specifically recruits Kif2A via the GCP2 subunit and its binding partner Mzt2. Hence, despite the long-standing view that γ-TuRC acts mainly as a microtubule template, we illustrate that its functional heterogeneity at the basal body facilitates both microtubule nucleation and Kif2A recruitment-mediated regulation of ciliogenesis, ensuring cell cycle progression. © 2022 The Author(s)

关键词： cell cycle ciliogenesis CP: Molecular biology kinesin motor microtubule primary cilium γ-tubulin ring complex

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