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Sialylation is involved in cell fate decision during development, reprogramming and cancer progression

Protein & Cell 2019年第8期10卷 550-565页

作者： Fenjie Li Junjun Ding Program in Stem Cell and Regenerative Medicine The Third Affiliated Hospital of Sun Yat-Sen University Zhongshan School of Medicine Sun Yat-Sen University Guangzhou China Key Laboratory for Stem Cells and Tissue Engineering Ministry of Education Department of Cell Biology Zhongshan School of Medicine Sun Yat-Sen University Guangzhou China

Sialylation, or the covalent addition of sialic acid to the terminal end of glycoproteins, is a biologically important modification that is involved in embryonic development, neurodevelopment, reprogramming, oncogenesis and immune responses. In this review, we have given a comprehensive overview of the current literature on the involvement of sialylation in cell fate decision during development, reprogramming and cancer progressionSialylation is essential for early embryonic development and the deletion of UDP-GIcNAc 2-epimerase, a rate-limiting enzyme in sialic acid biosynthesis, is embryonically lethal. Furthermore, the sialyltransferase ST6GAL1 is required for somatic cell reprogramming, and its downregulation is associated with decreased reprogramming efficiency. In addition, sialylation levels and patterns are altered during cancer progression, indicating the potential of sialylated molecules as cancer biomarkers. Taken together, the current evidences demonstrate that sialylation is involved in crucial cell fate decision.

关键词： sialylation cell fate development reprogramming cancer

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THE EFFECT OF TELE-YOGA ON PHYSICAL FITNESS AND MENTAL HEALTH OF IRRITABLE BOWEL SYNDROME DURING THE COVID-19 PANDEMIC

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Journal of Science and medicine in Sport 2023年 26卷 S120-S121页

作者： Chao, W. Chen, K. Cheng, B. Huang, C. National Chung Hsing University Program in Tissue Engineering and Regenerative Medicine Taiwan Show Chwan Memorial Hospital Orthopedics Taiwan National Chung Hsing University Graduate Institute of Biomedical Engineering Taiwan Cheng Ching Hospital Chunk Kang Branch Taiwan

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High-resolution dynamic imaging of chromatin DNA communication using Oligo-LiveFISH

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Cell 2025年第12期188卷 3310-3328.e27页

作者： Zhu, Yanyu Balaji, Ashwin Han, Mengting Andronov, Leonid Roy, Anish R. Wei, Zheng Chen, Crystal Miles, Leanne Cai, Sa Gu, Zhengxi Tse, Ariana Yu, Betty Chentzu Uenaka, Takeshi Lin, Xueqiu Spakowitz, Andrew J. Moerner, W.E. Qi, Lei S. Department of Bioengineering Stanford University Stanford 94305 CA United States Department of Chemistry Stanford University Stanford 94305 CA United States Biophysics PhD Program Stanford University Stanford 94305 CA United States Computational Biology Program Public Health Sciences Division and Translational Data Science IRC Fred Hutchinson Cancer Center Seattle 98109 WA United States Department of Chemical Engineering Stanford University Stanford 94305 CA United States Department of Materials Science and Engineering Stanford University Stanford 94305 CA United States Institute for Stem Cell Biology & Regenerative Medicine and Department of Pathology Stanford University School of Medicine Stanford 94305 CA United States Sarafan ChEM-H Stanford University Stanford 94305 CA United States Chan Zuckerberg Biohub San Francisco 94080 CA United States

Three-dimensional (3D) genome dynamics are crucial for cellular functions and disease. However, real-time, live-cell DNA visualization remains challenging, as existing methods are often confined to repetitive regions, suffer from low resolution, or require complex genome engineering. Here, we present Oligo-LiveFISH, a high-resolution, reagent-based platform for dynamically tracking non-repetitive genomic loci in diverse cell types, including primary cells. Oligo-LiveFISH utilizes fluorescent guide RNA (gRNA) oligo pools generated by computational design, in vitro transcription, and chemical labeling, delivered as ribonucleoproteins. Utilizing machine learning, we characterized the impact of gRNA design and chromatin features on imaging efficiency. Multi-color Oligo-LiveFISH achieved 20-nm spatial resolution and 50-ms temporal resolution in 3D, capturing real-time enhancer and promoter dynamics. Our measurements and dynamic modeling revealed two distinct modes of chromatin communication, and active transcription slows enhancer-promoter dynamics at endogenous genes like FOS. Oligo-LiveFISH offers a versatile platform for studying 3D genome dynamics and their links to cellular processes and disease. © 2025 Elsevier Inc.

关键词： CRISPR imaging DNA communication dynamic tracking enhancer-promoter interaction high-resolution imaging live DNA imaging non-repetitive genome imaging Oligo-LiveFISH polymer modeling primary cell

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Theranostic doxorubicin encapsulated FeAu alloy@metal-organic framework nanostructures enable magnetic hyperthermia and medical imaging in oral carcinoma

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Nanomedicine: Nanotechnology, Biology, and medicine 2023年 48卷 102652-102652页

作者： Dhawan, Udesh Tseng, Ching-Li Wu, Ping-Hsuan Liao, Mei-Yi Wang, Huey-Yuan Wu, Kevin C.-W. Chung, Ren-Jei Centre for the Cellular Microenvironment Division of Biomedical Engineering School of Engineering University of Glasgow GlasgowG12 8LT United Kingdom Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei City110 Taiwan International Ph. D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei City110 Taiwan Research Center of Biomedical Device College of Biomedical Engineering Taipei Medical University Taipei City110 Taiwan International Ph. D. Program in Cell Therapy and Regenerative Medicine College of Medicine Taipei Medical University Taipei City110 Taiwan Taipei106344 Taiwan Department of Applied Chemistry National Pingtung University Pingtung 90003 Taiwan Department of Stomatology MacKay Memorial Hospital Taipei104217 Taiwan Department of Chemical Engineering National Taiwan University Taipei10617 Taiwan Institute of Biomedical Engineering & Nanomedicine National Health Research Institute Keyan Road Zhunan Miaoli City350 Taiwan National Taiwan University Taipei106216 Taiwan

Metal-organic frameworks (MOFs) have emerged as attractive candidates in cancer theranostics due to their ability to envelop magnetic nanoparticles, resulting in reduced cytotoxicity and high porosity, enabling chemodrug encapsulation. Here, FeAu alloy nanoparticles (FeAu NPs) are synthesized and coated with MIL-100(Fe) MOFs to fabricate FeAu@MOF nanostructures. We encapsulated Doxorubicin within the nanostructures and evaluated the suitability of this platform for medical imaging and cancer theranostics. FeAu@MOF nanostructures (FeAu@MIL-100(Fe)) exhibited superparamagnetism, magnetic hyperthermia behavior and displayed DOX encapsulation and release efficiency of 69.95 % and 97.19 %, respectively, when stimulated with alternating magnetic field (AMF). In-vitro experiments showed that AMF-induced hyperthermia resulted in 90 % HSC-3 oral squamous carcinoma cell death, indicating application in cancer theranostics. Finally, in an in-vivo mouse model, FeAu@MOF nanostructures improved image contrast, reduced tumor volume by 30-fold and tumor weight by 10-fold, which translated to enhancement in cumulative survival, highlighting the prospect of this platform for oral cancer treatment. © 2023

关键词： Metal nanoparticles

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Development and Application of the Electrospun Microtube Array Membrane (MTAM) Substrate as a Potential Drug Encapsulation Platform for Continuous Drug Release Platform for Treatment of Elevated Intraocular Pressure (IOP) in Glaucoma Disease.

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Polymer 2025年

作者： Jou-Chen Huang Ching-Yu Lee Chee Ho Chew Wan-Ting Huang Shun-Chieh Chang Chien-Chung Chen Department of Ophthalmology Taipei Medical University Hospital Taipei Medical University Department of Ophthalmology School of Medicine College of Medicine Taipei Medical University Department of Orthopedics Taipei Medical University Hospital Taipei Medical University Department of Orthopedics School of Medicine College of Medicine Taipei Medical University Graduate Institute of Biomedical Materials and Tissue Engineering Taipei Medical University Taipei 11052 Taiwan International PhD Program for Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei 110 Taiwan The PhD Program for Translational Medicine Taipei Medical University Taipei 11052 Taiwan International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei 110 Taiwan Ph.D Program in Biotechnology Research and Development College of Pharmacy Taipei Medical University Taipei 110 Taiwan

Glaucoma is the leading cause of blindness which is characterized by the elevation of intraocular pressure (IOP) which results in optic nerve damage. Clinically, the current mainstay of treatment which involves the use of anti-glaucoma agents delivered in the form of topical eye drops have limitations such as short drug retention times, pulsatile delivery and localized adverse effects. In this work, we strive to demonstrate the development of a novel drug encapsulation device, known as Microtube Array Membrane (MTAM) as a potential substrate for encapsulation of clinically available anti-glaucoma agent that is based on the materials Polysulfone (PSF) and poly(lactic acid) (PLA) and poly(glycolic acid) (PLA-PLGA) copolymer. The resulting MTAM variants demonstrated tunable microstructures, mechanical properties and drug release; where pore sizes ranging from from 0.24 ± 0.02 μm to 17.62 ± 4.62 μm was successfully fabricated, and with loading efficiency of Brimonidine Tartrate up to 90%. Sustained drug release was observed over 3 days under simulated tear physiological conditions, with the PLA-PLGA MTAM variants released the greatest amount of drug encapsulated within and sustained even in the presence of simulated tears turnover. Critically, the encapsulation of the drug within the respective MTAMs seemed to mitigate any toxicity effects that was largely reported in direct use of Brimonidine Tartrate. Potentially, with more research and development, the MTAM based drug encapsulation could effective be deployed as a novel drug release system in future localized and sustained drug delivery.

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Small intestine submucosa as a growth factor attractor promotes peripheral nerve regeneration by enhancing syndecan-3/glial cell line-derived neurotrophic factor (GDNF) signalling: in vivo study * * Grant sponsor: The Ministry of Science and Technology (Taiwan);Grant number: 111-2320-B-005-009-MY3.

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Biomedical Materials (Bristol) 2023年第5期18卷 055002-055002页

作者： Liu, Chiung-Hui Chu, Yin-Hung Chen, Yin Hsiu Chiang, Yu Hsin Chen, Yu Hsuan Ku, Chung Yao Hsu, Min-Yen Lee, Yi-Ju Yang, Mao-Yi Liao, Wen-Chieh Doctoral Program in Tissue Engineering and Regenerative Medicine College of Medicine National Chung Hsing University No.145 Xingda Rd. South Dist Taichung40227 Taiwan Department of Post-Baccalaureate Medicine College of medicine National Chung Hsing University No.145 Xingda Rd. South Dist. Taichung City40227 Taiwan School of Medicine Chung Shan Medical University Taichung Taiwan. No.110 Sec.1 Jianguo N. Rd Taichung40201 Taiwan Department of Ophthalmology Chung Shan Medical University Hospital Taichung40201 Taiwan Department of Pathology Chung Shan Medical University Hospital Taichung40201 Taiwan Department of Pathology Chung Shan Medical University Taichung40201 Taiwan Department of Orthopedic Surgery Shin Kong Wu Ho-Su Memorial Hospital No. 95 Wen Chang Road Shih Lin District Taipei11101 Taiwan

Peripheral nerve regeneration (PNR) following trauma requires the reconstruction of the extracellular matrix (ECM) and the proper stimulation of growth factors. Decellularised small intestine submucosa (SIS) has been extensively used as an ECM scaffold for tissue repair, but its potential to enhance the effects of exogenous growth factors on PNR is not well understood. In this study, we evaluated the effects of SIS implantation combined with glial cell-derived growth factor (GDNF) treatment on PNR in a rat neurorrhaphy model. We found that both SIS and regenerating nerve tissue expressed syndecan-3 (SDC3), one of major heparan sulphate proteoglycans in nerve tissue, and that SDC3 interacted with GDNF in the regenerating nerve tissue. Importantly, the SIS-GDNF combined treatment enhanced the recovery of neuromuscular function and β3-tubulin-positive axonal outgrowth, indicating an increase in the number of functioning motor axons connecting to the muscle after neurorrhaphy. Our findings suggest that the SIS membrane offers a new microenvironment for neural tissue and promotes neural regeneration based on SDC3-GDNF signalling, providing a potential therapeutic approach for PNR. © 2023 IOP Publishing Ltd.

关键词： Cell culture

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TRPM1 promotes tumor progression in acral melanoma by activating the Ca 2+ /CaMKIIδ/AKT pathway

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Journal of Advanced Research 2023年 43卷 45-57页

作者： Chi-Che Hsieh Yue-Chiu Su Kuan-Ying Jiang Takamichi Ito Ting-Wei Li Yumiko Kaku-Ito Shih-Tsung Cheng Li-Tzong Chen Daw-Yang Hwang Che-Hung Shen National Institute of Cancer Research National Health Research Institutes Tainan 704 Taiwan Department of Pathology Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung 807 Taiwan Department of Dermatology Graduate School of Medical Sciences Kyushu University Fukuoka 812-8582 Japan Department of Life Sciences National Cheng Kung University Tainan 704 Taiwan Department of Dermatology Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung 807 Taiwan Department of Dermatology College of Medicine Kaohsiung Medical University Kaohsiung 807 Taiwan Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung 807 Taiwan Center for Cancer Research Kaohsiung Medical University Kaohsiung 807 Taiwan Ph.D. Program in Tissue Engineering and Regenerative Medicine Biotechnology Center National Chung Hsing University Taichung 402 Taiwan

Introduction Acral melanoma is a predominant and aggressive subtype of melanoma in non-Caucasian populations. There is a lack of genotype-driven therapies for over 50% of patients. TRPM1 (transient receptor potential melastatin 1), a nonspecific cation channel, is mainly expressed in retinal bipolar neurons and skin. Nonetheless, the function of TRPM1 in melanoma progression is poorly understood. Objectives We investigated the association between TRPM1 and acral melanoma progression and revealed the molecular mechanisms by which TRPM1 promotes tumor progression and malignancy. Methods TRPM1 expression and CaMKII phosphorylation in tumor specimens were tested by immunohistochemistry analysis and scored by two independent investigators. The functions of TRPM1 and CaMKII were assessed using loss-of-function and gain-of-function approaches and examined by western blotting, colony formation, cell migration and invasion, and xenograft tumor growth assays. The effects of a CaMKII inhibitor, KN93, were evaluated using both in vitro cell and in vivo xenograft mouse models. Results We revealed that TRPM1 protein expression was positively associated with tumor progression and shorter survival in patients with acral melanoma. TRPM1 promoted AKT activation and the colony formation, cell mobility, and xenograft tumor growth of melanoma cells. TRPM1 elevated cytosolic Ca 2+ levels and activated CaMKIIδ (Ca 2+ /calmodulin-dependent protein kinase IIδ) to promote the CaMKIIδ/AKT interaction and AKT activation. The functions of TRPM1 in melanoma cells were suppressed by a CaMKII inhibitor, KN93. Significant upregulation of phospho-CaMKII levels in acral melanomas was related to increased expression of TRPM1. An acral melanoma cell line with high expression of TRPM1, CA11, was isolated from a patient to show the anti-tumor activity of KN93 in vitro and in vivo . Conclusions TRPM1 promotes tumor progression and malignancy in acral melanoma by activating the Ca 2+/ CaMKIIδ/AKT pathway.

关键词： Acral melanoma TRPM1 CaMKII Ca 2+ channel

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Assessment of circulating extracellular vesicles from calorie-restricted mice and humans in ischaemic injury models

Journal of Extracellular Biology

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Journal of Extracellular Biology 2023年第5期2卷 e86页

作者： Jaimes, Manuel S. V. Liao, Chia-Te Chen, Max M. Czosseck, Andreas Lee, Tsung-Lin Chou, Yu-Hsiang Chen, Yung-Ming Lin, Shuei-Liong Lai, James J. Lundy, David J. Graduate Institute of Biomedical Materials & Tissue Engineering Taipei Medical University Taipei Taiwan Division of Nephrology Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei Taiwan Division of Nephrology Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan TMU Research Center of Urology and Kidney (TMU-RCUK) Taipei Medical University Taipei Taiwan Division of Nephrology Department of Internal Medicine National Taiwan University Hospital College of Medicine National Taiwan University Taipei Taiwan Graduate Institute of Physiology College of Medicine National Taiwan University Taipei Taiwan Department of Bioengineering University of Washington Seattle WA United States Department of Materials Science and Engineering National Taiwan University of Science and Technology Taipei Taiwan International PhD Program in Biomedical Engineering Taipei Medical University Taipei Taiwan Center for Cell Therapy Taipei Medical University Hospital Taipei Taiwan

Calorie restriction (CR) and fasting affect lifespan, disease susceptibility and response to acute injury across multiple animal models, including ischaemic injuries such as myocardial infarction or kidney hypoxia. The cargo and function of circulating extracellular vesicles (EV) respond to changes in host physiology, including exercise, injury, and other interventions. Thus, we hypothesised that EVs induced following CR may reflect some of the beneficial properties of CR itself. In a pilot study, EVs were isolated from mice following 21 days of 30 % CR, and from eight human donors after 72 h water-only fasting. EV size, concentration and morphology were profiled by NTA, western blot and cryoEM, and their function was assessed using multiple assays related to ischaemic diseases. We found that EVs from post-fasting samples better protected cardiac cells from hypoxia/reperfusion (H/R) injury compared to pre-fasting EVs. However, there was no difference when used to treat H/R-injured kidney epithelial cells. Post-fasting derived EVs slowed the rate of fibroblast migration and slightly reduced macrophage inflammatory gene expression compared to pre-fasting derived EVs. Lastly, we compared miRNA cargos of pre- and post-fasting human serum EVs and found significant changes in a small number of miRNAs. We conclude that fasting appears to influence EV cargo and function, with varied effects worthy of further exploration. © 2023 The Authors. Journal of Extracellular Biology published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.

关键词： calorie restriction cardiomyocyte diet extracellular vesicle fasting hypoxia ketone macrophage microRNA serum

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CCL5 Protects Cortical Neuron Function by Regulating M2 Microglia Activation After Mild Traumatic Brain Injury

SSRN

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SSRN 2022年

作者： Tsai, Yih-Jeng Ho, Man-Hau Yen, Chia-Hung Wang, Jia-Yi Burnouf, Thierry Chen, Chia-Yen Wang, Yun Chiang, Yung-Hsiao Hoffer, Barry J. Chou, Szu-Yi Department of Otolaryngology Head and Neck Surgery Shin Kong Wu HoSu Memorial Hospital Taipei Taiwan School of Medicine Fu Jen Catholic University New Taipei City Taiwan Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University National Health Research Institute Taiwan Graduate Institute of Neural Regenerative Medicine College of Medical Science and Technology Taipei Medical University Taipei Taiwan Department of Biological Science and Technology National Pingtung University of Science and Technology Neipu Pingtung91201 Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei11031 Taiwan Department of Neurosurgery Taipei Medical University Hospital Taipei11031 Taiwan Neuroscience Research Center Taipei Medical University Taipei11031 Taiwan International PhD Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei Taiwan NeuroTMULille International Laboratory Taipei Medical University Taipei Taiwan International PhD Program in Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei Taiwan Brain and Consciousness Research Centre TMU Shuang Ho Hospital New Taipei City Taiwan Center for Neuropsychiatric Research National Health Research Institutes Zhunan Miaoli County Taiwan Department of Surgery School of Medicine College of Medicine Taipei Medical University 11031 Taiwan Department of Neurosurgery Case Western Reserve University School of Medicine ClevelandOH United States Scientist Emeritus National Institutes of Health United States International Master Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University Taipei Taiwan

Cytokines and chemokines play important roles in inflammation and repair following brain injury. M1 microglia are pro-inflammatory which produce cytokines and lead to neural injury;in contrast, M2 microglia are anti-inflammatory, release neurotrophic factors, and promote neural repair processes. Chemokine CCL5, increased after TBI, shows a neuroprotective function by reducing oxidative stress. CCL5 may contribute to the balance between oxidative stress and immune responses after brain injury. Herein, we investigated the role of CCL5 in microglial polarization after mild traumatic brain injury, focusing on the cerebral cortex.C57BL/6 and CCL5 knockout (CCL5-KO) mice were given a mild traumatic brain injury (TBI) using weight-drop. Neurological parameters such as motor and sensory functions were analyzed by mNSS score, accelerating rotarod, beam walking, and adhesive removal tests. Oxidative stress and neuron damage were measured by NADPH oxidase activity, hypoxyloprobe staining and FJC. Performance of motor and sensory functions in both WT and CCL5-KO mice were impaired after brain injury which recovered after 7 days-post-injury (dpi) in the WT group but only after 14 days in the CCL5-KO mouse group. RT-qPCR analysis revealed that pro-inflammation cytokines - IL-1β, TNF-α, and IL-6 were higher in CCL5-KO mice compared to WT mice at 4 and 14 dpi. In contrast, M2-like microglia markers - IL-10 and Agr-1 were increased in WT mouse cortical tissue at 4 dpi. Oxidative stress increased both M1 and M2- related cytokine expression in BV2 cells treated with H 2 O 2;CCL5 treatment increased M2- but suppressed M1- related cytokine gene activation. Intranasal delivery of CCL5 reduced neuronal oxidative stress, increased IL-10 expression and improved motor and sensory functions in CCL5-KO mice after brain *** summary, CCL5, which alters immune responses and protects neurons from TBI damage, has an important function in regulating M2-like microglial polarization during post-

关键词： Polarization

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Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain (vol 86, pg 511, 2020)

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NATURE NEUROSCIENCE 2020年第10期23卷 1308-1308页

作者： Marschallinger, Julia Iram, Tal Zardeneta, Macy Lee, Song E. Lehallier, Benoit Haney, Michael S. Pluvinage, John V. Mathur, Vidhu Hahn, Oliver Morgens, David W. Kim, Justin Tevini, Julia Felder, Thomas K. Wolinski, Heimo Bertozzi, Carolyn R. Bassik, Michael C. Aigner, Ludwig Wyss-Coray, Tony Department of Neurology and Neurological Sciences School of Medicine Stanford University Stanford CA USA Paul F. Glenn Center for the Biology of Aging Stanford University School of Medicine Stanford CA USA Institute of Molecular Regenerative Medicine Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS) Paracelsus Medical University Salzburg Austria Department of Genetics School of Medicine and Chemistry Engineering and Medicine for Human Health (ChEM-H) Stanford University Stanford CA USA Medical Scientist Training Program Stanford University School of Medicine Stanford CA USA Department of Chemistry Stanford ChEM-H and Howard Hughes Medical Institute Stanford University Stanford CA USA Department of Laboratory Medicine Paracelsus Medical University Salzburg Austria Obesity Research Unit Paracelsus Medical University Salzburg Austria Institute of Molecular Biosciences BioTechMed-Graz University of Graz Graz Austria Stanford Neurosciences Institute Stanford University Stanford CA USA Department of Veterans Affairs Palo Alto CA USA

Microglia become progressively activated and seemingly dysfunctional with age, and genetic studies have linked these cells to the pathogenesis of a growing number of neurodegenerative diseases. Here we report a striking buildup of lipid droplets in microglia with aging in mouse and human brains. These cells, which we call ‘lipid-droplet-accumulating microglia’ (LDAM), are defective in phagocytosis, produce high levels of reactive oxygen species and secrete proinflammatory cytokines. RNA-sequencing analysis of LDAM revealed a transcriptional profile driven by innate inflammation that is distinct from previously reported microglial states. An unbiased CRISPR–Cas9 screen identified genetic modifiers of lipid droplet formation; surprisingly, variants of several of these genes, including progranulin (GRN), are causes of autosomal-dominant forms of human neurodegenerative diseases. We therefore propose that LDAM contribute to age-related and genetic forms of neurodegeneration.

关键词： Cellular neuroscience Cognitive ageing Glial biology

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