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Dynamic transcriptional programs define distinct mammalian cortical lineages

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Neural Regeneration Research 2024年第2期19卷 387-389页

作者： Tanzila Mukhtar Verdon Taylor department of Biomedicine University of BaselBaselSwitzerland Eli and Edythe Broad center of Regeneration Medicine and stem cell Research University of CaliforniaSan FranciscoCAUSA

The cerebral cortex is composed of billions of neurons and glia that are generated sequentially during corticogenesis.These cells are generated in an organized fashion during development.At early stages of brain devel... 详细信息

关键词： cortex cerebral development

Use of induced pluripotent stem cell-derived brain cells,organoids,assembloids,and blood-brain barrier models in understanding alcohol and anesthetic-induced brain injuries:an emerging perspective

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Neural Regeneration Research 2024年第5期19卷 953-954页

作者： Xiaowen Bai department of cell biology Neurobiology&AnatomyMedical College of WisconsinMilwaukeeWIUSA

Neurological disorders,including developmental disorders,Alzheimer’s disease(AD),and psychiatric conditions,have significant social and economic impacts globally.Despite extensive research into the underlying mechanisms of these disorders,effective treatments remain elusive,partly due to the complexity of the brain,the limited availability of human brain tissue,and the blood-brain barrier(BBB)’s impermeability to certain drugs.This perspective article discusses the potential of human induced pluripotent stem cell(iPSC)-based models of brain cells,organoids,assembloids,and BBB to advance our understanding of the etiology,progression,and mechanisms of brain injuries induced by alcohol consumption and general anesthesia.These models could also be used to develop protective and therapeutic approaches.

关键词： injuries protective drugs

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 diseases.However,the molecular mechanisms underlying neuromuscular dysfunction are currently unclear.Recent studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle maintenance.In 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 Hb9-Cre.mnKO exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and lethality.Prmt1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve injury.The transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and mitochondria.Consistently,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor neurons.Furthermore,Prmt1 inhibition in motor neurons elicited mitochondrial dysfunction.Our findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle loss.Thus,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

An effective pharmacological hydrogel induces optic nerve repair and improves visual function

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Science China(Life Sciences) 2024年第3期67卷 529-542页

作者： Lipeng Wang Shan Zhang Yawen Han Shuo Tang Jiarui Li Lina Bu Dongyu Zhao Hongkui Deng department of cell biology Schoolof Basic Medical SciencesPeking University Stem Cell Research CenterStateKey Laboratoryof Naturaland Biomimetic DrugsPeking University Health Science Center Beijing 100191China MOE Key Laboratory of cell Proliferation and Differentiation College of Life SciencesPeking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China Academy for Advanced Interdisciplinary Studies Peking UniversityBeijing 100871China Changping Laboratory Beijing 102206China department of Ophthalmology Peking University People's Hospital Eye Diseases and Optometry InstituteBeijing 100871China department of Biomedical Informatics School of Basic Medical SciencesPeking UniversityBeijing 100191China

Irreversible eye lesions, such as glaucoma and traumatic optic neuropathy, can cause blindness;however, no effective treatments exist. The optic nerve, in particular, lacks the capacity to spontaneously regenerate, requiring the development of an effective approach for optic nerve repair, which has proven challenging. Here, we demonstrate that a combination of the small molecules 3BDO and trichostatin A(TSA)—which regulate mTOR and HDAC, respectively—packaged in thermosensitive hydrogel for 4-week-sustained release after intravitreal injection, effectively induced optic nerve regeneration in a mouse model of optic nerve crush injury. Moreover, this combination of 3BDO and TSA also protected axon projections and improved visual responses in an old mouse model(11 months old) of glaucoma. Taken together, our data provide a new, local small molecule-based treatment for the effective induction of optic nerve repair, which may represent a foundation for the development of pharmacological methods to treat irreversible eye diseases.

关键词： retinal ganglion cell axon regeneration old-age glaucoma small molecules pharmacological hydrogel visual function repair

Foundation models in molecular biology

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Biophysics Reports 2024年第3期10卷 135-151页

作者： Yunda Si Jiawei Zou Yicheng Gao Guohui Chuai Qi Liu Luonan Chen Key Laboratory of Systems Health Science of Zhejiang Province School of Life Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai Institute of Biochemistry and cell biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences University of Chinese Academy of Sciences Translational Medical center for stem cell Therapy and Institute for Regenerative Medicine Shanghai East Hospital Frontier Science Center for Stem Cell Research Bioinformatics Department School of Life Sciences and Technology Tongji University Shanghai Research Institute for Intelligent Autonomous Systems

Determining correlations between molecules at various levels is an important topic in molecular biology. Large language models have demonstrated a remarkable ability to capture correlations from large amounts of data in the field of natural language processing as well as image generation, and correlations captured from data using large language models can also be applicable to solving a wide range of specific tasks, hence large language models are also referred to as foundation models. The massive amount of data that exists in the field of molecular biology provides an excellent basis for the development of foundation models, and the recent emergence of foundation models in the field of molecular biology has really pushed the entire field forward. We summarize the foundation models developed based on RNA sequence data, DNA sequence data, protein sequence data, single-cell transcriptome data, and spatial transcriptome data respectively, and further discuss the research directions for the development of foundation models in molecular biology.

关键词： Foundation models Molecular biology Transcriptome

CRISPR,CAR-T,and NK:Current applications and future perspectives

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Genes & Diseases 2024年第4期11卷 246-257页

作者： Mohadeseh Khoshandam Hossein Soltaninejad Amir Ali Hamidieh Saman Hosseinkhani department of Reproductive biology Academic Center for EducationCultureand Research(ACECR)Qom branch***Iran National Institute of Genetic Engineering and Biotechnology(NIGEB) Tehran 14965/161Iran department of stem cells technology and Tissue Regeneration Faculty of Interdisciplinary Science and TechnologiesTarbiat Modares UniversityTehran 15614Iran Pediatric cell Therapy and Gene Therapy Research center GeneCell&Tissue Research InstituteTehran University of Medical SciencesTehran ***Iran department of Biochemistry Faculty of Biological SciencesTarbiat Modares UniversityTehran 15614Iran

Chimeric antigen receptor T(CAR-T)cell therapy represents a breakthrough in personalized cancer treatments.In this regard,synthetic receptors comprised of antigen recognition domains,signaling,and stimulatory domains are used to reprogram T-cells to target tum or cells and destroy them.Despite the success of this approach in refractory B-cell malignancies,the optimal potency of CAR T-cell therapy for many other cancers,particularly solid tumors,has not been validated.Natural killer cells are powerful cytotoxic lymphocytes specialized in recognizing and dispensing the tumor cells in coordination with other anti-tumor immunity cells.Based on these studies,many investigations are focused on the accurate designing of CAR T-cells with clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system or other novel gene editing tools that can induce hereditary changes with or without the presence of a double-stranded break into the genome.These methodologies can be specifically focused on negative controllers of T-cells,induce modifications to a particular gene,and produce reproducible,safe,and powerful allogeneic CAR T-cells for on-demand cancer immunotherapy.The improvement of the CRISPR/Cas9 innovation offers an adaptable and proficient gene-editing capability in activating different pathways to help natural killer cells interact with novel CARs to particularly target tumor cells.Novel achievements and future challenges of combining next-generation CRISPR-Cas9 gene editing tools to optimize CAR T-cell and natural killer cell treatment for future clinical trials toward the foundation of modern cancer treatments have been assessed inthis review.

关键词： Cancer CAR T-cell CRISPR Gene editing Immunotherapy NK cell

Effect of Aqueous-Alcoholic Extract of Ducrosia Anethifolia Boiss on the Fetal Liver of Diabetic Rats

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 104-113页

作者： Hossein Kargar Jahromi Farangis Ghasemi Elmira Mikaeiliagah Research center for Noncommunicable Diseases Jahrom University of Medical SciencesJahromIran department of biology Islamic Azad UniversityJahromIran department of biology Ardabil BranchIslamic Azad UniversityArdabilIran stem cell and Tissue Engineering Laboratory Department of OrthopaedicsWest Virginia UniversityMorgantownUSA

Objective:Moshgak(Ducrosia anethifolia)is a wild plant with medicinal value.The present study aimed to evaluate the effect of Moshgak on the liver tissue of the diabetic rat fetus.Materials and Methods:In this animal study,the aqueous-alcoholic extract of Moshgak was prepared in the standard method.Forty rats were divided randomly into five groups,including control,sham,and three diabetic groups.The rats were diabetic with intraperitoneal injection of a single dose of streptozotocin(80 mg)and 2 diabetic groups were treated with Moshgak extract(280 and 560 mg/kg/bw)for 19 days.The rats were anesthetized and their blood was taken to measure the blood glucose,insulin,and malondialdehyde.Then,their fetuses were removed.The fetal liver sections were obtained by using the stereological methods.The micrometry of the liver tissue was performed and data were analyzed.Results:The finding showed a statistically significant increase(Pcell count hepatic decreased in the treated groups.Furthermore,the changes in blood glucose,malondialdehyde,and insulin in diabetic rats were improved significantly by Moshgak treatment.The dilation of sinusoids,hepatocyte vacuolation,and mild lymphocytosis was observed in all diabetic groups except the treatment group with Moshgak 560 mg/kg/bw.Conclusions:According to obtained results,Moshgak extract was able to compensate partially the changes induced by diabetes in the fetal liver tissue.Therefore,due to the side effects of diabetes during pregnancy,further research on anti-diabetic properties of Moshgak is suggested.

关键词： Diabetes Ducrosia anethifolia hepatocyte insulin micrometry rat

Aberrant LETM1 elevation dysregulates mitochondrial functions and energy metabolism and promotes lung metastasis in osteosarcoma

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Genes & Diseases 2024年第3期11卷 368-384页

作者： Yulu Shi Quan Kang Hong Zhou Xiaohan Yue Yang Bi Qing Luo stem cell biology and Therapy Laboratory The Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400014China department of Pediatric Surgery The Children's Hospital of Chongqing Medical UniversityChongqing 400014China

Osteosarcoma is a differentiation-deficient disease,and despite the unique advan-tages and great potential of differentiation therapy,there are only a few known differentia-tion inducers,and little research has been done on their targets.cell differentiation is associated with an increase in mitochondrial content and activity.The metabolism of some tu-mor cells is characterized by impaired oxidative phosphorylation,as well as up-regulation of aerobic glycolysis and pentose phosphate pathways.Leucine-containing zipper and EF-hand transmembrane protein 1(LETM1)is involved in the maintenance of mitochondrial morphology and is closely associated with tumorigenesis and progression,as well as cancer cell stemness.We found that MG63 and 143B osteosarcoma cells overexpress LETM1 and exhibit abnormalities in mitochondrial structure and function.Knockdown of LETM1 partially restored the mitochon-drial structure and function,inhibited the pentose phosphate pathway,promoted oxidative phosphorylation,and led to osteogenic differentiation.It also inhibited spheroid cell forma-tion,proliferation,migration,and invasion in an in vitro model.When LETM1 was knocked down in vivo,there was reduced tumor formation and lung metastasis.These data suggest that mitochondria are aberrant in LETM1-overexpressing osteosarcoma cells,and knockdown of LETM1 partially restores the mitochondrial structure and function,inhibits the pentose phosphate pathway,promotes oxidative phosphorylation,and increases osteogenic differentiation,thereby reducing malignant biological behavior of the cells.

关键词： Cancer metabolism Differentiation LETM1 Osteosarcoma stemness

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 posture.Disturbances in motor functions constitute the main body of CP symptoms.These symptoms surface in early childhood and patients are affected for the rest of their lives.Currently,treatment involves various pharmacotherapies for different types of CP,including antiepileptics for epilepsy and Botox A for focal spasticity.However,none of these methods can provide full symptom relief.This 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 safety.AIM To analyze the efficacy and safety of MSCT in CP patients.METHODS Our sample consists of four CP patients who cannot stand or walk without external support.All 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)instruments.We utilized the Modified Ashworth Scale(MAS)to measure spasticity.RESULTS We found significant improvements in MAS scores after the intervention on both sides.Two 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=0.046.However,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,and it partially improves motor functions.

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