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Recent progress of principal techniques used in the study of Müller glia reprogramming in mice

Cell Regeneration 2024年第1期13卷 39-54页

作者： Zhiyuan Yin Jiahui Kang Haoan Xu Shujia Huo Haiwei Xu Key Lab of Visual Damage and Regeneration&Restoration of Chongqing Southwest Eye HospitalSouthwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038P.R.China School of Life Sciences and Technology Tongji UniversityShanghai 200092China

In zebrafish,Müller glia(MG)cells retain the ability to proliferate and de-differentiate into retinal progenitor-like cells,subsequently differentiating into retinal neurons that can replace those damaged or lost due to retinal *** con-trast,the reprogramming potential of MG in mammals has been lost,with these cells typically responding to retinal damage through *** efforts have been dedicated to achieving the reprogramming of MG cells in ***,significant advancements have been achieved in reprogramming MG cells in mice employing various *** the same time,some inevitable challenges have hindered identifying accurate MG cell reprogramming rather than the illusion,let alone improving the reprogramming efficiency and maturity of daughter ***,several strategies,including lineage tracking,multi-omics techniques,and functional analysis,have been developed to investigate the MG reprogramming process in *** review summarizes both the advantages and limitations of these novel strategies for analyzing MG reprogramming in mice,offering insights into enhancing the reliability and efficiency of MG reprogramming.

关键词： Müller glia reprogramming Retina Mice Multi-omics Technique

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Generation of an Induced Pluripotent Stem Cell Line, ICGi043-A, by reprogramming Peripheral Blood Mononuclear Cells from a Parkinson's Disease Patient with p.G2019S Mutation in the LRRK2 Gene

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RUSSIAN JOURNAL OF DEVELOPMENTAL BIOLOGY 2023年第1期54卷 72-79页

作者： Grigor'eva, E. V. Pavlova, S. V. Malakhova, A. A. Yarkova, E. S. Sorogina, D. A. Minina, J. M. Miliukhina, I. V. Nikolaev, M. A. Pchelina, S. N. Medvedev, S. P. Zakian, S. M. Russian Acad Sci Inst Cytol & Genet Siberian Branch Novosibirsk 630090 Russia Russian Acad Sci Bekhtereva Inst Human Brain St Petersburg 197376 Russia Pavlov First St Petersburg State Med Univ Pavlov First St St Petersburg 197022 Russia

The pathological variant p.G2019S in the LRRK2 gene leads to the occurrence of a hereditary form of Parkinson's disease (PD) and affects 7% of patients with a familial form of the disease. However, the mechanisms that trigger pathological events during the development of the disease are not yet fully understood. The authors obtained iPSCs (ICGi043-A line) from peripheral blood mononuclear cells of a patient with a hereditary form of PD associated with the genetic variant c.6055G>A (p.G2019S, rs34637584) in the LRRK2 gene using transfection with episomal vectors. iPSCs rapidly proliferate in dense monolayer cell colonies, are positive for endogenous alkaline phosphatase, have a normal karyotype (46,XX), express pluripotency markers (OCT4, SOX2, NANOG, TRA-1-60, SSEA-4), and are capable to differentiate into three germ layers (ecto-, endo-, and mesoderm), which confirms their pluripotent status. Future directed differentiation of the obtained iPSCs into dopaminergic neurons will allow the creation of an in vitro cell model of PD associated with the pathological variant c.6055G>A in the LRRK2 gene and contribute to understanding the pathogenesis of PD.

关键词： Parkinson's disease induced pluripotent stem cells polymorphisms reprogramming

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Generation of an Induced Pluripotent Stem Cell Line, ICGi042-A, by reprogramming Peripheral Blood Mononuclear Cells from a Parkinson's Disease Patient with c.1000G>A Mutation in the LRRK2 Gene

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RUSSIAN JOURNAL OF DEVELOPMENTAL BIOLOGY 2023年第1期54卷 80-87页

作者： Grigor'eva, E. V. Pavlova, S. V. Malakhova, A. A. Medvedev, S. P. Minina, J. M. Vyatkin, Y. V. Khabarova, E. A. Rzaev, J. A. Kovalenko, L. V. Zakian, S. M. Russian Acad Sci Inst Cytol & Genet Siberian Branch Novosibirsk 630090 Russia Minist Hlth Russian Federat Meshalkin Natl Med Res Ctr Novosibirsk 630055 Russia Russian Acad Sci Inst Chem Biol & Fundamental Med Siberian Branch Novosibirsk 630090 Russia Novosibirsk State Univ Novosibirsk 630090 Russia FSBI Fed Neurosurg Ctr Novosibirsk 630087 Russia Khanty Mansiysk Autonomous Okrug Ugra Surgut State Surgut 628403 Russia

The search for new polymorphisms associated with hereditary diseases is important for diagnostics and the study of the disease's development pathology. The authors have analyzed a clinical exome of a Parkinson's disease patient and identified single-nucleotide variations in the LRRK2 (c.1000G>A, c.2167A>G) and PINK1 (c.1562A>C) genes. The LRRK2:c.1000G>A mutation has uncertain clinical significance and is interesting for further investigation. We generated induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells (PBMCs) of the patient by nonintegrating episomal vectors. iPSCs demonstrate typical morphology and normal karyotype (46,XY), express pluripotency markers (OCT4, SOX2, NANOG, SSEA4, TRA-1-60), and are able to produce derivatives of three germ layers.

关键词： Parkinson's disease induced pluripotent stem cells polymorphisms reprogramming

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Polyaminoglycoside-mediated cell reprogramming system for the treatment of diabetes mellitus

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JOURNAL OF CONTROLLED RELEASE 2022年 343卷 420-433页

作者： Pan, Yunqi Shao, Meiyu Li, Pan Xu, Chen Nie, Jingjun Zhang, Kai Wu, Sen Sui, Dandan Xu, Fu-Jian Beijing Univ Chem Technol Key Lab Biomed Mat Nat Macromolecules Coll Mat Sci & EngnBeijing Lab Biomed Mat State Key Lab Chem Resource EngnMinist Educ Beijing Peoples R China China Agr Univ Coll Biol Sci Beijing Adv Innovat Ctr Food Nutr & Human Hlth State Key Lab Agrobiotechnol Beijing Peoples R China

Diabetes mellitus is a disease of metabolism, featuring persistent hyperglycaemia due to insufficient insulin secretion or insulin resistance. At present, the generation of new beta cells from autologous cells by ectopic expression of specific transcription factors is a promising treatment for diabetes. The application of this strategy urgently needs safe and effective gene delivery vectors. In this work, a therapeutic plasmid (pNPMN-PBase), combined multiple specific transcription factors Ngn3, Pdx1, Mafa and Neruod1 (NPMN), was firstly constructed. Then, phenylboronic acid (PBA)-functionalized branched polymers (SS-HPT-P) have been proposed to deliver pNPMN-PBasefor the promising treatment of diabetes. SS-HPT-P had good biocompatibility and low cytotoxicity, and could achieve liver-targeted delivery. SS-HPT-P/pNPMN-PBase system can effectively realize the liver delivery of exogenous therapeutic genes, induce the reprogramming of hepatocytes into beta-like cells, reestablish the endogenous insulin-expression system, and alleviate diabetes and its complications. The present study thus provides an effective strategy for the cell replacement therapy of diabetes.

关键词： Diabetes reprogramming Phenylboronic acid Vector Liver-targeted Gene therapy

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Self-Delivery Ternary Bioregulators for Photodynamic Amplified Immunotherapy by Tumor Microenvironment reprogramming

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ACS NANO 2022年第1期16卷 1182-1197页

作者： Zhao, Lin-Ping Zheng, Rong-Rong Kong, Ren-Jiang Huang, Chu-Yu Rao, Xiao-Na Yang, Ni Chen, A-Li Yu, Xi-Yong Cheng, Hong Li, Shi-Ying Guangzhou Med Univ Key Lab Mol Target & Clin Pharmacol Guangzhou 511436 Peoples R China Guangzhou Med Univ Sch Pharmaceut Sci State Key Lab Resp Dis Guangzhou 511436 Peoples R China Guangzhou Med Univ Affiliated Hosp 5 Guangzhou 511436 Peoples R China Southern Med Univ Sch Biomed Engn Biomat Res Ctr Guangzhou 510515 Peoples R China Guangdong Pharmaceut Univ Affiliated Hosp Clin Med 5 Guangzhou 510080 Peoples R China

Abnormal metabolism of cancer cells results in complex tumor microenvironments (TME), which play a dominant role in tumor metastasis. Herein, self-delivery ternary bioregulators (designated as TerBio) are constructed for photodynamic amplified immunotherapy against colorectal cancer by TME reprogramming. Specifically, carrier-free TerBio are prepared by the self-assembly of chlorine e6, SB505124 (SB), and lonidamine (Lon), which exhibit improved tumor accumulation, tumor penetration, and cellular uptake behaviors. Interestingly, TerBio-mediated photodynamic therapy (PDT) could not only inhibit the primary tumor growth but also induce immunogenic cell death of tumors to activate the cascade immune response. Furthermore, TerBio are capable of TME reprograming by SB-triggered transforming growth factor (TGF)-beta blockage and Lon-induced lactic acid efflux inhibition. As a consequence, TerBio significantly suppresses distant and metastatic tumor growth by PDT-amplified immunotherapy. This study might advance the development of self-delivery nanomedicine against malignant tumor growth and metastasis.

关键词： self-delivery immunotherapy photodynamic therapy reprogramming tumor microenvironment

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Creation of Induced Pluripotent Stem Cells ICGi044-B and ICGi044-C Using reprogramming of Peripheral Blood Mononuclear Cells of a Patient with Parkinson's Disease Associated with c.1492T>G Mutation in the GLUD2 Gene

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RUSSIAN JOURNAL OF DEVELOPMENTAL BIOLOGY 2023年第1期54卷 104-111页

作者： Sorogina, D. A. Grigor'eva, E. V. Malakhova, A. A. Pavlova, S. V. Medvedev, S. P. Vyatkin, Y. V. Khabarova, E. A. Rzaev, J. A. Zakian, S. M. Russian Acad Sci Inst Cytol & Genet Siberian Branch Novosibirsk 630090 Russia Novosibirsk State Univ Novosibirsk 630090 Russia FSBI Fed Neurosurg Ctr Novosibirsk 630087 Russia

Parkinson's disease is a multifactorial disease;both genetic predisposition (5% of all cases), environmental factors, and age-related changes in the brain and other body systems contribute to its etiology. For the diagnosis and study of the pathology of the disease development, it is important to search for new polymorphisms associated with hereditary forms of the disease. The clinical exome of a 55-year-old patient with Parkinson's disease was analyzed and a single nucleotide polymorphism in the GLUD2 gene (c.1492T>G) was identified. This genetic variant is pathogenic according to the ClinVar database, but the mechanism of pathogenesis is still poorly understood. In addition, there are currently no relevant models based on human cells, which is of great interest. We generated induced pluripotent stem cells (iPSCs) from patient peripheral blood mononuclear cells using nonintegrating episomal vectors expressing OCT4, KLF4, L-MYC, SOX2, LIN28, and p53 shRNA. The obtained iPSC lines (ICGi044-B and ICGi044-C) demonstrate typical ESC-like morphology, normal karyotype (46,XY), express pluripotency markers (OCT4, SOX2, NANOG, SSEA4, TRA-1-60), and are able to give derivatives of three germ layers. The iPSC lines ICGi044-B and ICGi044-C, as well as their neural derivatives, represent a unique in vitro cell model for studying the pathogenetic mechanisms of the development of Parkinson's disease associated with the c.1492T>G mutation in the GLUD2 gene.

关键词： reprogramming induced pluripotent stem cells Parkinson's disease polymorphisms

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H3K36 methylation is a reprogramming barrier

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NATURE CELL BIOLOGY 2023年第8期25卷 1077-1078页

作者： Cohen, Lea Rachel Zehava Meshorer, Eran Hebrew Univ Jerusalem Edmond & Lily Safra Ctr Brain Sci Jerusalem Israel Hebrew Univ Jerusalem Alexander Silberman Inst Life Sci Dept Genet Jerusalem Israel

reprogramming of somatic cells is an inherently inefficient process. A new study has now identified histone H3K36 methylation as a crucial reprogramming barrier that operates downstream of TGF beta signalling. Global inhibition of H3K36 methylation induced PRC2-dependent silencing of mesenchymal genes and dramatically increased reprogramming efficiency.

关键词： reprogramming

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reprogramming the Metabolome of Centella asiatica (L.) Urban Callus: Profiling of Newly Synthesized Cryptic Anthocyanins Triggered by LED Light Exposure

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Phyton-International Journal of Experimental Botany 2025年第4期94卷 1269-1286页

作者： Claude Y.Hamany Djande Paul A.Steenkamp Ian A.Dubery Research Centre for Plant Metabolomics Department of BiochemistryUniversity of JohannesburgAuckland ParkP.O.Box 524Johannesburg2006South Africa

Centella asiatica L.,a medicinal herb,has attracted substantial interest in research as well as commercial domains due to its bioactive compounds which include the pentacyclic triterpenoid centellosides,and in addition,*** addition,hydroxycinnamic acid conjugates as well as *** latter is the major class of secondary plant metabolites and comprises various subclasses,including *** are rarely reported in extracts from *** and differ structurally due to a flavylium(2-phenylchromenylium)ion that carries a positive charge at the oxygen atom of the C-ring of the basic flavonoid *** of *** was initiated and propagated on synthetic media and subjected to different light *** callus resulted from white fluorescent illumination,while purple callus developed in response to white light emitting diode(LED)*** profile the metabolites responsible for the intense purple coloration,methanolic extracts were prepared from the two cell *** phenolic,flavonoid,and anthocyanin content were determined and indicated(i)very low levels of flavonoids and anthocyanins in white callus and(ii)that anthocyanins dominate the flavonoid content of the purple *** were subjected to untargeted ultra-high-performance liquid chromatography coupled to high-definition mass spectrometry(UHPLC–MS)to profile newly synthesized *** annotation was based on accurate mass determination and characteristic fragmentation ***,the reprogramming of the metabolome of white *** callus due to LED illumination is reported and the profiles of cryptic anthocyanins as well as putative flavonoid and caffeoylquinic acid co-pigments in purple callus are described.

关键词： Anthocyanins callus Centella asiatica cryptic flavonoids liquid chromatography mass spectrometry reprogramming

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Harnessing stem cell and lineage reprogramming technology to treat cardiac fibrosis

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Cell Regeneration 2023年第1期12卷 1-14页

作者： Ni Zeng Wei Tang Yanghong Wu Hang Fan Shuanglun Xie Nan Cao Advanced Medical Technology Center The First Affiliated HospitalZhongshan School of MedicineSun Yat-Sen UniversityGuangdong 510080China NHC Key Laboratory of Assisted Circulation(Sun Yat-Sen University) Guangdong 510080China Key Laboratory for Stem Cells and Tissue Engineering(Sun Yat-Sen University) Ministry of EducationGuangdong 510080China Department of Cardiology Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangdong 510120China

Cardiac fibrosis is a pathological response characterized by excessive deposition of fibrous connective tissue within the *** typically occurs following cardiac injuries or ***,the lack of suitable models for disease modeling and high-throughput drug discovery has hindered the establishment of an effective treatments for cardiac *** emergence and rapid progress of stem-cell and lineage reprogramming technology offer an unprecedented opportunity to develop an improved humanized and patient-specific model for studying cardiac fibrosis,providing a platform for screening potential drugs and synchronously elucidating the underlying molecular ***,reprogramming cardiac fibroblasts into cardiomyocyte-like cells to reduce scar volume and induce myocardial tissue regeneration is a promising approach in treating cardiac *** this review,we summarize the current advancements in stem cell technologies applied to study cardiac fibrosis and provide insights for future investigations into its mechanisms,drug discovery as well as therapy method.

关键词： Cardiac fibrosis Stem cell Disease modelling Drug screening Transplantation reprogramming

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Direct cardiac reprogramming comes of age: Recent advance and remaining challenges

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SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY 2022年第0期122卷 37-43页

作者： Xie, Yifang Liu, Jiandong Qian, Li Univ N Carolina McAllister Heart Inst Dept Pathol & Lab Med Chapel Hill NC 27599 USA

The adult human heart has limited regenerative capacity. As such, the massive cardiomyocyte loss due to myocardial infarction leads to scar formation and adverse cardiac remodeling, which ultimately results in chronic heart failure. Direct cardiac reprogramming that converts cardiac fibroblast into functional cardiomyocyte-like cells (also called iCMs) holds great promise for heart regeneration. Cardiac reprogramming has been achieved both in vitro and in vivo by using a variety of cocktails that comprise transcription factors, microRNAs, or small molecules. During the past several years, great progress has been made in improving reprogramming efficiency and understanding the underlying molecular mechanisms. Here, we summarize the direct cardiac reprogramming methods, review the current advances in understanding the molecular mechanisms of cardiac reprogramming, and highlight the novel insights gained from single-cell omics studies. Finally, we discuss the remaining challenges and future directions for the field.

关键词： ICM reprogramming Fibroblast Myocardial infarction

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