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Unresolved Excess Accumulation of Myelin-Derived Cholesterol Contributes to Scar Formation after Spinal Cord Injury

research 2024年第1期2023卷 17-32页

作者： Bolin Zheng Yijing He Shuai Yin Xu Zhu Qing Zhao Huiyi Yang Zhaojie wang Rongrong Zhu Liming Cheng Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration Ministry of EducationDepartment of OrthopedicsTongji HospitalSchool of MedicineTongji UniversityShanghai 200092China Frontier Science center for stem cell research School of Life Science and TechnologyTongji UniversityShanghai 200092China Clinical center for Brain and Spinal Cord research Tongji UniversityShanghai 200092China

Spinal cord injury triggers complex pathological cascades,resulting in destructive tissue damage and incomplete tissue *** formation is generally considered a barrier for regeneration in the central nervous ***,the intrinsic mechanism of scar formation after spinal cord injury has not been fully ***,we report that excess cholesterol accumulates in phagocytes and is inefficiently removed from spinal cord lesions in young adult ***,we observed that excessive cholesterol also accumulates in injured peripheral nerves but is subsequently removed by reverse ***,preventing reverse cholesterol transport leads to macrophage accumulation and fibrosis in injured peripheral ***,the neonatal mouse spinal cord lesions are devoid of myelin-derived lipids and can heal without excess cholesterol *** found that transplantation of myelin into neonatal lesions disrupts healing with excessive cholesterol accumulation,persistent macrophage activation,and *** internalization suppresses macrophage apoptosis mediated by CD5L expression,indicating that myelin-derived cholesterol plays a critical role in impaired wound *** together,our data suggest that the central nervous system lacks an efficient approach for cholesterol clearance,resulting in excessive accumulation of myelin-derived cholesterol,thereby inducing scar formation after injury.

关键词： healing Spinal impaired

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Loss of Tet hydroxymethylase activity causes mouse embryonic stem cell differentiation bias and developmental defects

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Science China(Life Sciences) 2024年第10期67卷 2132-2148页

作者： Mengting Wang Liping Wang Yanxin Huang Zhibin Qiao Shanru Yi Weina Zhang Jing Wang Guang Yang Xinyu Cui Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang Shaorong Gao Jiayu Chen Clinical and Translational research center of Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Shanghai Tenth People’s Hospital School of MedicineTongji UniversityShanghai 200072China Frontier Science center for stem cell research Tongji UniversityShanghai 200092China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education Orthopaedic Department of Tongji HospitalTongji UniversityShanghai 200065China Shanghai Institute of stem cell research and Clinical Translation Shanghai 200120China

The TET family is well known for active DNA demethylation and plays important roles in regulating transcription,the epigenome and ***,previous studies using knockdown(KD)or knockout(KO)models to investigate the function of TET have faced challenges in distinguishing its enzymatic and nonenzymatic roles,as well as compensatory effects among TET family members,which has made the understanding of the enzymatic role of TET not accurate *** solve this problem,we successfully generated mice catalytically inactive for specific Tet members(Tetm/m).We observed that,compared with the reported KO mice,mutant mice exhibited distinct developmental defects,including growth retardation,sex imbalance,infertility,and perinatal ***,Tetm/mmouse embryonic stem cells(mESCs)were successfully established but entered an impaired developmental program,demonstrating extended pluripotency and defects in ectodermal differentiation caused by abnormal DNA ***,Tet3,traditionally considered less critical for m ESCs due to its lower expression level,had a significant impact on the global hydroxymethylation,gene expression,and differentiation potential of ***,there were common regulatory regions between Tet1 and Tet3 in pluripotency *** summary,our study provides a more accurate reference for the functional mechanism of Tet hydroxymethylase activity in mouse development and ESC pluripotency regulation.

关键词： Tet hydroxymethylase activity mESCs DNA demethylation 5hmC

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Coiled-coil domain-containing 38 is required for acrosome biogenesis and fibrous sheath assembly in mice

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Journal of Genetics and Genomics 2024年第4期51卷 407-418页

作者： Yaling Wang Xueying Huang Guoying Sun Jingwen Chen Bangguo Wu Jiahui Luo Shuyan Tang Peng Dai Feng Zhang Jinsong Li Lingbo Wang Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Institute of Reproduction and Development Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Shanghai Key Laboratory of Maternal and Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China State Key Laboratory of cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China

During spermiogenesis,haploid spermatids undergo dramatic morphological changes to form slender sperm flagella and cap-like acrosomes,which are required for successful *** deformities in flagella cause a male infertility syndrome,multiple morphological abnormalities of the flagella(MMAF),while acrosomal hypoplasia in some cases leads to sub-optimal embryonic developmental ***,evidence regarding the occurrence of acrosomal hypoplasia in MMAF is ***,we report the generation of base-edited mice knocked out for coiled-coil domain-containing 38(Ccdc38)via inducing a nonsense mutation and find that the males are *** Ccdc38-KO sperm display acrosomal hypoplasia and typical MMAF *** find that the acrosomal membrane is loosely anchored to the nucleus and fibrous sheaths are disorganized in Ccdc38-KO *** analyses reveal that Ccdc38 knockout causes a decreased level of TEKT3,a protein associated with acrosome biogenesis,in testes and an aberrant distribution of TEKT3 in *** finally show that intracytoplasmic sperm injection overcomes Ccdc38-related *** study thus reveals a previously unknown role for CCDC38 in acrosome biogenesis and provides additional evidence for the occurrence of acrosomal hypoplasia in MMAF.

关键词： Acrosomal hypoplasia Multiple morphological abnormalities of the flagella(MMAF) Infertility Sperm motility Asthenoteratozoospermia Disease modeling

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Ethical concerns in aging research:perspectives of global frontline researchers

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Science China(Life Sciences) 2024年第10期67卷 2149-2156页

作者： Yaojin Peng Lulu Ding Zhenyu Xiao Moshi Song Jianwei Lv Guang-Hui Liu Key Laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Stem Cell and Reproductive BiologyInstitute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Beijing Institute for stem cell and Regenerative Medicine Beijing 100101China Institute for stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China Aging Biomarker Consortium(ABC) Beijing 100101China School of Life Science Beijing Institute of TechnologyBeijing 100081China School of Life Sciences Xiamen UniversityXiamen 361102China Advanced Innovation center for Human Brain Protection and National Clinical research center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijing 100053China Aging Translational Medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China

This study investigated the ethical landscape of aging research amid the increasing global focus on extending the human lifespan and health *** global survey of 180 researchers across 38 jurisdictions revealed divergent perceptions of aging,a consensus regarding the feasibility of delaying aging,and multiple perspectives regarding lifespan *** present findings underscore a paradigm shift toward inclusive and ethically sound research,emphasizing the need for an approach that strikes a balance between basic and clinical *** addition,this study highlighted key ethical concerns in aging research,including the effects of misleading advertising,potential inequality in access to aging interventions,and risks pertaining to the extrapolation of research findings from lower-model organisms to *** insights presented in this paper call for an integrated approach for overcoming the complex ethical and societal challenges in aging research to ensure responsible and equitable advancements in this burgeoning field.

关键词： aging ethical landscape ethics surveys and questionnaires

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Allogeneic mesenchymal stem cells may be a viable treatment modality in cerebral palsy

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World Journal of Clinical Cases 2024年第9期12卷 1585-1596页

作者： Osman Boyalı Serdar Kabatas ErdinçCivelek Omer Ozdemir Yeliz Bahar-Ozdemir Necati Kaplan Eyüp Can Savrunlu Erdal Karaöz Department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34360Turkey center for stem cell&Gene Therapy research and Practice University of Health Sciences TurkeyIstanbul 34360Turkey Department of Physical Medicine and Rehabilitation Health Sciences University Sultan Abdulhamid Han Training and Research HospitalIstanbul 34668Turkey Department of Neurosurgery Istanbul Rumeli UniversityÇorlu Reyap HospitalTekirdağ59860Turkey Department of Neurosurgery Nevşehir State HospitalNevşehir 50300Turkey center for Regenerative Medicine and stem cell research&Manufacturing(LivMedcell) Liv HospitalIstanbul 34340Turkey Department of Histology and Embryology Istinye UniversityFaculty of Medicineİstanbul 34010Turkey center for stem cell and Tissue Engineering research and Practice Istinye UniversityIstanbul 34340Turkey

BACKGROUND Cerebral palsy(CP)describes a group of disorders affecting movement,balance,and *** in motor functions constitute the main body of CP *** symptoms surface in early childhood and patients are affected for the rest of their ***,treatment involves various pharmacotherapies for different types of CP,including antiepileptics for epilepsy and Botox A for focal ***,none of these methods can provide full symptom *** has prompted researchers to look for new treatment modalities,one of which is mesenchymal stem cell therapy(MSCT).Despite being a promising tool and offering a wide array of possibilities,mesenchymal stem cells(MSCs)still need to be investigated for their efficacy and *** To analyze the efficacy and safety of MSCT in CP *** Our sample consists of four CP patients who cannot stand or walk without external *** of these cases received allogeneic MSCT six times as 1×106/kg intrathecally,intravenously,and intramuscularly using umbilical cord-derived MSCs(UC-MSC).We monitored and assessed the patients pre-and post-treatment using the Wee Functional Independence Measure(WeeFIM),Gross Motor Function Classification System(GMFCS),and Manual Ability Classification Scale(MACS)*** utilized the Modified Ashworth Scale(MAS)to measure *** We found significant improvements in MAS scores after the intervention on both *** months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;four months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;12 months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=***,there was no significant difference in motor functions based on WeeFIM results(P>0.05).GMFCS and MACS scores differed significantly at 12 months after the intervention(P=0.046,P=0.046).Finally,there was no significant change in cognitive functions(P>0.05).CONCLUSION In light of our findings,we believe that UC-MSC therapy has a positive effect on spasticity

关键词： Cerebral palsy Mesenchymal stem cell Transplantation Wharton’s jelly Muscle spasticity

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Unveiling the anticancer effect of traditional Chinese herbal medicine

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World Journal of Gastroenterology 2024年第30期30卷 3625-3627页

作者： Naoki Asano Division of Carcinogenesis and Senescence Biology Tohoku University Graduate School of MedicineNatori 981-1293MiyagiJapan Division of Cancer stem cell Miyagi Cancer Center Research InstituteNatori 981-1293MiyagiJapan

In this issue of World Journal of Gastroenterology,Huang et al reported that Calculus bovis(CB),a traditional Chinese herbal medicine,impedes the growth of liver cancers in *** further in vitro studies,they showed that CB suppressed the M2 polarization of tumor-associated macrophages by suppressing the Wnt signaling pathway,which consequently inhibited the growth of liver *** the effects of traditional Chinese herbal medicine are often not scientifically proven,Huang et al successfully identified the molecular mechanism involved in the anticancer effect of CB,and it is anticipated that the molecular mechanisms involved in the effects of other traditional Chinese herbal medicines will be scientifically elucidated,as demonstrated in this article.

关键词： Calculus bovis Chinese herbal medicine Wnt Hepatocellular carcinoma Liver cancer Tumor-associated macrophages M2 polarization

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Protein Arginine Methyltransferase 1 Ablation in Motor Neurons Causes Mitochondrial Dysfunction Leading to Age-related Motor Neuron Degeneration with Muscle Loss

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research 2024年第1期2023卷 637-649页

作者： Hyun-Kyung So Hyebeen Kim Jinwoo Lee Chang-Lim You Chae-Eun Yun Hyeon-Ju Jeong Eun-Ju Jin Yunju Jo Dongryeol Ryu Gyu-Un Bae Jong-Sun Kang Department of Molecular cell Biology Sungkyunkwan University School of MedicineSuwonKorea Single cell Network research center Sungkyunkwan University School of MedicineSuwonKorea research Institute of Aging-Related Diseases AniMusCureInc.SuwonKorea Drug Information research Institute Muscle Physiome Research CenterCollege of PharmacySookmyung Women’s UniversitySeoulKorea

Neuromuscular dysfunction is tightly associated with muscle wasting that occurs with age or due to degenerative ***,the molecular mechanisms underlying neuromuscular dysfunction are currently *** studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle *** the current study,we set out to determine the role of Prmt1 in neuromuscular function by generating mice with motor neuron-specific ablation of Prmt1(mnKO)using *** exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and ***1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve *** transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and ***,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor ***,Prmt1 inhibition in motor neurons elicited mitochondrial *** findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle ***,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

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Immune rebalancing at the maternal-fetal interface of maternal SARS-CoV-2 infection during early pregnancy

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Protein & cell 2024年第6期15卷 460-473页

作者： Chenxiang Xi Zihui Yan Dandan Bai Yalin Zhang Beiying Wang Xiaoxiao Han Li Wu Xiaohui Shi Zhiyi Hu Ming Tang Zhongqu Su Yingdong Liu Binya Liu Jiqing Yin Hong Wang Xiaocui Li Yanping Zhang Shaorong Gao Wenqiang Liu Shanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalShanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Jiaxing Maternity and Child Health Care Hospital Jiaxing 314050China

The current coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)remains a threat to pregnant ***,the impact of early pregnancy SARS-CoV-2 infection on the maternal-fetal interface remains poorly ***,we present a comprehensive analysis of single-cell transcriptomics and metabolomics in placental samples infected with SARS-CoV-2 during early *** to control placentas,SARS-CoV-2 infection elicited immune responses at the maternal-fetal interface and induced metabolic alterations in amino acid and phospholipid profiles during the initial weeks ***,subsequent immune cell activation and heightened immune tolerance in trophoblast cells established a novel dynamic equilibrium that mitigated the impact on the maternal-fetal ***,the immune response and metabolic alterations at the maternal-fetal interface exhibited a gradual decline during the second *** study underscores the adaptive immune tolerance mechanisms and establishment of immunological balance during the first two trimesters following maternal SARS-CoV-2 infection.

关键词： fetal alterations pregnancy

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Effects of exosomes from mesenchymal stem cells on functional recovery of a patient with total radial nerve injury: A pilot study

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World Journal of stem cells 2024年第1期16卷 19-32页

作者： ErdinçCivelek Serdar Kabatas Eyüp Can Savrunlu Furkan Diren Necati Kaplan Demet Ofluoğlu Erdal Karaöz Department of Neurosurgery University of Health SciencesGaziosmanpaşa Training and Research HospitalGaziosmanpaşa 34255IstanbulTurkey Department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalGaziosmanpaşa 34255IstanbulTurkey center for stem cell&Gene Therapy research and Practice University of Health Sciences TurkeyGaziosmanpaşa 34255IstanbulTurkey Department of Neurosurgery Nevşehir State HospitalNevşehir 50300Turkey Department of Neurosurgery Istanbul Rumeli UniversityÇorlu Reyap HospitalÇorlu 59860TekirdağTurkey Department of Physical Medicine and Rehabilitation Ofluoğlu KlinikGöztepe 34728IstanbulTurkey Liv Hospital Center for Regenerative Medicine and Stem Cell Research&Manufacturing(LivMedCell)Beşiktaş34340IstanbulTurkey Department of Histology and Embryology Istinye UniversityFaculty of MedicineZeytinburnu 34010IstanbulTurkey Istinye University Center for Stem Cell and Tissue Engineering Research and PracticeBeşiktaş34340IstanbulTurkey

BACKGROUND Peripheral nerve injury can result in significant clinical complications that have uncertain ***,there is a lack of effective pharmacological interventions for nerve damage,despite the existence of several small compounds,Despite the objective of achieving full functional restoration by surgical intervention,the persistent challenge of inadequate functional recovery remains a significant concern in the context of peripheral nerve *** To examine the impact of exosomes on the process of functional recovery following a complete radial nerve *** A male individual,aged 24,who is right-hand dominant and an immigrant,arrived with an injury caused by a knife *** cut is located on the left arm,specifically below the *** neurological examination and electrodiagnostic testing reveal evidence of left radial nerve *** sural autograft was utilized for repair,followed by the application of 1 mL of mesenchymal stem cell-derived exosome,comprising 5 billion *** exosome was split into four equal volumes of 0.25 mL each and delivered microsurgically to both the proximal and distal stumps using the subepineural *** patient was subjected to a period of 180 d during which they had neurological examination and electrodiagnostic *** The duration of the patient’s follow-up period was 180 *** increasing Tinel’s sign and sensory-motor recovery were detected even at the 10th wk following nerve *** the conclusion of the 6-mo post-treatment period,an evaluation was conducted to measure the extent of improvement in motor and sensory functions of the *** assessment was based on the British Medical research Council scale and the Mackinnon-Dellon *** results indicated that the level of improvement in motor function was classified as M5,denoting an excellent ***,the level of improvement in sensory function was classified as S3+,indicating a good *** is

关键词： Mesenchymal stem cell Exosomes Radial nerve Sural nerve

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Improve meat production and virus resistance by simultaneously editing multiple genes in livestock using Cas12i^(Max)

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Science China(Life Sciences) 2024年第3期67卷 555-564页

作者： Jilong Ren Tang Hai Yangcan Chen Ke Sun Zhiqiang Han Jing Wang Chongyang Li Qingwei Wang Leyun Wang Huabing Zhu Dawei Yu Wei Li Shanjiang Zhao State Key Laboratory of Animal Nutrition Key Laboratory of Animal GeneticsBreeding and Reproduction of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijing 100193China State Key Laboratoryf stem cell and Reproductive Biology Instituteof ZooogyChinese Academyof SciencesBeijing 100101China Beijing Institute for stem cell and Regenerative Medicine Beijing 100101China Beijing Farm Animal research center Institute of ZoologyChinese Academy of SciencesBeijing 100101China

The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated gene(Cas) system is continually optimized to achieve the most efficient gene editing effect. The Cas12i^(Max), a Cas12i variant, exhibits powerful DNA editing activity and enriches the gene editing toolbox. However, the application of Cas12i^(Max)in large domestic animals has not yet been reported. To verify the efficiency and feasibility of multiple gene editing in large animals, we generated porcine fibroblasts with simultaneous knockouts of IGF2, ANPEP, CD163,and MSTN via Cas12i^(Max)in one step. Phenotypically stable pigs were created through somatic cell nuclear transfer technology. They exhibited improved growth performance and muscle quality. Furthermore, we simultaneously edited three genes in bovine fibroblasts. A knockout of MSTN and PRNP was created and the amino acid Q-G in CD18 was precisely substituted. Meanwhile, no off-target phenomenon was observed by sum-type analysis or off-target detection. These results verified the effectiveness of Cas12i^(Max)for gene editing in livestock animals and demonstrated the potential application of Cas12i^(Max)in the field of animal trait improvement for agricultural production.

关键词： Cas12i^(Max) gene editing livestock multiple trait improvement

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