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differentiation and functional connectivity of fetal tectal transplants

Neural Regeneration Research 2023年第11期18卷 2325-2331页

作者： Alan R.Harvey School of Human Sciences The University of Western AustraliaLions Eye Instituteand Perron Institute for Neurological and Translational ScienceNedlandsWAAustralia

Data from studies analyzing the differentiation and functional connectivity of embryo nic neural tissue grafted into the mammalian nervous system has led to the clinical testing of the fetal graft approach in patients with neurodegenerative disease.While some success has been achieved,ethical concerns have led to a search for alternative therapeutic strategies,mostly exploring the use of neural precursors or neurons derived from pluripotent stem cells to replace damaged host neurons and restore lost circuitries.These more recent studies address questions of graft viability,differentiation,and connectivity similar to those posed by researchers in earlier fetal transplant work,thus reviews of the fetal graft literature may inform and help guide ongoing research in the stem cell/organoid field.This brief review describes some key observations from research into the transplantation of neural tissue into the rat visual syste m,focusing on grafts of the fetal supe rior colliculus(tectal grafts) into neonatal or adult hosts.In neonate hosts,grafts quickly develop connections with the underlying host mid b rain and attain a morphology typical of mature grafts by about 2 weeks.G rafts consistently contain numerous localized regions which,based on neurofibrillar staining,neuronal morphology(Golgi),neurochemistry,receptor expression,and glial architecture,are homologous to the stratum griseum supe rficiale of normal superior colliculus.These localized "patches" are also seen after explant culture and when donor tectal tissue is dissociated and reaggregated prior to transplantation.In almost all circumstances,host retinal innervation is restricted to these localized patches,but only those that are located adjacent to the graft surfa ce.Synapses are formed and there is evidence of functional drive.The only exception occurs when Schwann cells are added to dissociated tecta prior to reaggregation.In these co-grafts,the peripheral glia appear to compete with local target fa ctors and host retinal ingrowth is more widespread.Othe

关键词： axon regeneration differentiation embyronic grafts fetal tissue neural precursors retinotectal stem cells superior colliculus synaptogenesis transplantation

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differentiation of retinal ganglion cells from induced pluripotent stem cells: a review

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International Journal of Ophthalmology(English edition) 2019年第1期12卷 152-160页

作者： Shang-Li Ji Shi-Bo Tang Aier Eye Institute Aier School of Ophthalmology Central South University

Glaucoma is a common optic neuropathy that is characterized by the progressive degeneration of axons and the loss of retinal ganglion cells(RGCs). Glaucoma is one of the leading causes of irreversible blindness worldwide. Current glaucoma treatments only slow the progression of RGCs loss. Induced pluripotent stem cells(iPSCs) are capable of differentiating into all three germ layer cell lineages. iPSCs can be patient-specific,making iPSC-derived RGCs a promising candidate for cell replacement. In this review, we focus on discussing the detailed approaches used to differentiate iPSCs into RGCs.

关键词： glaucoma retinal ganglion cells induced pluripotent stem cells differentiation

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differentiation of human olfactory mucosa mesenchymal stem cells into photoreceptor cells in vitro

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International Journal of Ophthalmology(English edition) 2017年第10期10卷 1504-1509页

作者： Wen Lu Da Duan Zacharia Ackbarkhan Ming Lu Min-Li Huang Department of Ophthalmology the First Affiliated Hospital of Guangxi Medical University Department of Neurosurgery the 163rd Hospital of Chinese PLAthe Second Affiliated Hospital of Hunan Normal University

AIM：To investigate whether the human olfactory mucosa mesenchymal stem cells（OM-MSCs）can differentiate into photoreceptor cells in vitro.METHODS：Through the olfactory mucosa adherent method,olfactory mucosa was isolated,cultured and identified in vitro among mesenchymal stem cells.The cell surface markers were analyzed by flow cytometry,induced to differentiate into retinal photoreceptor cells in vitro,and the expression of rhodopsin was observed and identified by Immunofluorescence and Western blot methods.RESULTS：OM-MSCs from human were spindle cellbased,and showing radial colony arrangement.OM-MSCs were negative for CD34,CD45 and CD105,but positive for CD73 and CD90.Following induction,a strong positive reaction was produced by photoreceptor specific marker rhodopsin in the cells.CONSLUSION：This novel finding demonstrates that OM-MSCs can be cultured and expanded in vitro.They possess biological characteristics of mesenchymal stem cells,and have the ability to be induced into retinal cells.

关键词： human olfactory mucosa mesenchymal stemcells differentiation retinal cells

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Poly-L-ornithine blocks the inhibitory effects of fibronectin on oligodendrocyte differentiation and promotes myelin repair

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Neural Regeneration Research 2023年第4期18卷 832-839页

作者： Ya-Jie Xiong Shahid Hussain Soomro Zhong-Hai Huang Pan-Pan Yu Jie Ping Hui Fu Department of Anatomy School of Basic Medical SciencesWuhan UniversityWuhanHubei ProvinceChina Guangdong-Hongkong-Macao Institute of CNS Regeneration Ministry of Education Joint International Research Laboratory of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina Department of Pharmacology School of Basic Medical SciencesWuhan UniversityWuhanHubei ProvinceChina

The extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain.In many cases,the microenvironment surrounding demyelination lesions contains inhibitory molecules,which lead to repair failure.Accordingly,blocking the activity of these inhibitory factors in the extracellular matrix should lead to more successful remyelination.In the central nervous system,oligodendrocytes form the myelin sheath.We performed primary cell culture and found that a natural increase in fibronectin promoted the proliferation of oligodendrocyte progenitors during the initial stage of remyelination while inhibiting oligodendrocyte differentiation.Poly-L-ornithine blocked these inhibitory effects without compromising fibronectin’s pro-proliferation function.Experiments showed that poly-L-ornithine activated the Erk1/2 signaling pathway that is necessary in the early stages of differentiation,as well as PI3K signaling pathways that are needed in the mid-late stages.When poly-L-ornithine was tested in a lysolecithin-induced animal model of focal demyelination,it enhanced myelin regeneration and promoted motor function recovery.These findings suggest that poly-L-ornithine has the potential to be a treatment option for clinical myelin sheath injury.

关键词： differentiation Erk1/2 extracellular matrix fibronectin lysolecithin-induced demyelination oligodendrocyte PI3K poly-L-ornithine proliferation remyelination

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Deciphering the chromatin spatial organization landscapes during BMMSC differentiation

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Journal of Genetics and Genomics 2023年第4期50卷 264-275页

作者： Zhaowei Teng Yun Zhu Da Lin Qinggang Hao Qiaoning Yue Xiaochao Yu Shuo Sun Lihong Jiang Sheng Lu Department of Orthopedics The First People's Hospital of Yunnan ProvinceAffiliated Hospital of Kunming University of Science and TechnologyKunmingYunnan 650032China Key Laboratory of Yunnan Provincial Innovative Application of Traditional Chinese Medicine The First People's Hospital of Yunnan ProvinceKunmingYunnan 650032China Clinical Medical Research Center The First People's Hospital of Yunnan ProvinceKunmingYunnan 650032China The Sixth Affiliated Hospital of Kunming Medical University YuxiYunnan 653100China State Key Laboratory of Agricultural Microbiology Huazhong Agricultural UniversityWuhanHubei 430070China Center for Life Sciences School of Life SciencesYunnan UniversityKunmingYunnan 650504China

The differentiation imbalance in bone marrow mesenchymal stem cells(BMMSCs)is critical for the development of bone density diseases as the population ages.BMMSCs are precursor cells for osteoblasts and adipocytes;however,the chromatin organization landscapes during BMMSC differentiation remain elusive.In this study,we systematically delineate the four-dimensional genome and dynamic epigenetic atlas of BMMSCs by RNA sequencing,assay for transposase-accessible chromatin sequencing,and highthroughput chromosome conformation capture.The structure analyses reveal 17.5%common and28.5%-30%specific loops among BMMSCs,osteoblasts,and adipocytes.The subsequent correlation of genome-wide association studies and expression quantitative trait locus(e QTL)data with multi-omics analysis reveal 274 genes and 3634 single nucleotide polymorphisms(SNPs)associated with bone degeneration and osteoporosis(OP).We hypothesize that SNP mutations affect transcription factor(TF)binding sites,thereby affecting changes in gene expression.Furthermore,26 motifs,260 TFs,and 291SNPs are identified to affect the e QTL.Among these genes,DAAM2,TIMP2,and TMEM241 are found to be essential for diseases such as bone degeneration and OP and may serve as potential drug targets.

关键词： Bone marrow mesenchymal stem cells differentiation Hi-C ATAC-Seq Single nucleotide polymorphisms Genome-wide association studies

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The developmental changes in intestinal epithelial cell proliferation,differentiation,and shedding in weaning piglets

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Animal Nutrition 2022年第2期9卷 214-222页

作者： Min Wang Lixia Wang Xian Tan Lei Wang Xia Xiong Yancan Wang Qiye Wang Huansheng Yang Yulong Yin Hunan International Joint Laboratory of Animal Intestinal Ecology and Health Laboratory of Animal Nutrition and Human HealthCollege of Life SciencesHunan Normal UniversityChangsha 410081HunanChina Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry ProductionKey Laboratory of Agro-ecological Processes in Subtropical RegionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125HunanChina

Intestinal epithelial homeostasis plays an important role in intestinal morphology and function.However,the developmental changes in intestinal epithelial cell turnover in piglets during early weaning are unknown so far.Thus,the aim of this work was to detect changes in piglet gut development from weaning to post-weaning d 14.Accordingly,40 piglets were used in the present study,and 8 piglets were randomly selected for sampling at d 0,1,3,7 and 14 post-weaning,respectively.The results showed that weaning stress significantly affected small intestinal morphological architecture,and this impact was the worst on d 3,and then returned to normal on d 14.Furthermore,the number of the marker of proliferation Ki-67(Ki67)positive cells was decreased on d 1 and 3,and then recovered on d 14(Pdifferentiation(Pdifferentiation and shedding,and the mTOR signaling pathway was involved in this process.Our findings provide a cellular mechanism for intestinal developmental changes during weaning periods.This may provide nutritionists with better insight into designing efficient in-feed alternatives for preventing the unfavorable gut development in weaning piglets.

关键词： Intestinal epithelial cell Proliferation differentiation Shedding Weaning piglet

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differentiation therapy:a promisingstrategy for cancer treatment

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Chinese Journal of Cancer 2016年第1期35卷 1-3页

作者： Min Yan Quentin Liu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer Center510060 GuangzhouGuangdongP.R.China Institute of Cancer Stem Cell Cancer CenterDalian Medical University116044 DalianLiaoningP.R.China

Poor differentiation is an important hallnnark of cancer cells,and differentiation therapy holds great promise for cancer treatment.The restoration of IkB kinase a(IKKa)leads to the differentiation of nasopharyngeal carcinoma cells with reduced tumorigenicity.The findings by Yan et al.validate the polycomb protein enhancer of zeste homologue2(EZH2)as a target for intervention.

关键词： differentiation therapy, Cancer treatment, IkB kinase α

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miR-103-3p targets Ndel1 to regulate neural stem cell proliferation and differentiation

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Neural Regeneration Research 2022年第2期17卷 401-408页

作者： Wen Li Shan-Shan Wang Bo-Quan Shan Jian-Bing Qin He-Yan Zhao Mei-Ling Tian Hui He Xiang Cheng Xin-Hua Zhang Guo-Hua Jin Department of Human Anatomy Institute of NeurobiologyNantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education NantongJiangsu ProvinceChina Co-Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

The regulation of adult neural stem cells(NSCs) is critical for lifelong neurogenesis. MicroRNAs(miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signaling networks responsible for several cellular processes. In this study, mi R-103-3 p was transfected into neural stem cells derived from embryonic hippocampal neural stem cells. The results showed that mi R-103-3 p suppressed neural stem cell proliferation and differentiation, and promoted apoptosis. In addition, mi R-103-3 p negatively regulated Nud E neurodevelopment protein 1-like 1(Ndel1) expression by binding to the 3′ untranslated region of Ndel1. Transduction of neural stem cells with a lentiviral vector overexpressing Ndel1 significantly increased cell proliferation and differentiation, decreased neural stem cell apoptosis, and decreased protein expression levels of Wnt3 a, β-catenin, phosphor-GSK-3β, LEF1, c-myc, c-Jun, and cyclin D1, all members of the Wnt/β-catenin signaling pathway. These findings suggest that Ndel1 is a novel mi R-103-3 p target and that mi R-103-3 p acts by suppressing neural stem cell proliferation and promoting apoptosis and differentiation. This study was approved by the Animal Ethics Committee of Nantong University, China(approval No. 20200826-003) on August 26, 2020.

关键词： apoptosis canonical Wnt pathway differentiation MiR-103-3p Ndel1 neural stem cells neurogenesis proliferation

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differentiation renders susceptibility to excitotoxicity in HT22 neurons

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Neural Regeneration Research 2013年第14期8卷 1297-1306页

作者： Minchao He Jun Liu haowu Cheng Yigang Xing William Z Suo Department of Neurology Sun Yat-sen Memorial HospitalSun Yat-sen University Laboratory for Alzheimer's Disease & Aging Research Veterans Affairs Medical Center Department of Neurology University of Kansas Medical Center Molecular & Integrative Physiology University of Kansas Medical Center

HT22 is an immortalized mouse hippocampal neuronal cell line that does not express cholinergic and glutamate receptors like mature hippocampal neurons in vivo. This in part prevents its use as a model for mature hippocampal neurons in memory-related studies. We now report that HT22 cells were appropriately induced to differentiate and possess properties similar to those of mature hippocampal neurons in vivo, such as becoming more glutamate-receptive and excitatory. Results showed that sensitivity of HT22 cells to glutamate-induced toxicity changed dramatically when comparing undifferentiated with differentiated cells, with the half-effective concentration for differentiated cells reducing approximately two orders of magnitude. Moreover, glutamate-induced toxicity in differentiated cells, but not undifferentiated cells, was inhibited by the N-methyi-D- aspartate receptor antagonists MK-801 and memantine. Evidently, differentiated HT22 cells expressed N-methyI-D-aspartate receptors, while undifferentiated cells did not. Our experimental findings indicated that differentiation is important for immortalized cell lines to render post-mitotic neuronal properties, and that differentiated HT22 neurons represent a better model of hippocampal neurons than undifferentiated cells.

关键词： neural regeneration brain injury HT22 differentiation N-methyI-D-aspartate receptor glutamateexcitatory neurotoxicity mitosis hippocampus neurons MK-801＂ memantine grants-supportedpaper neuroregeneration

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Nutritional stimulation by in-ovo feeding modulates cellular proliferation and differentiation in the small intestinal epithelium of chicks

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Animal Nutrition 2022年第1期8卷 91-101页

作者： Naama Reicher Tal Melkman-Zehavi Jonathan Dayan Eric AWong Zehava Uni Department of Animal Science The Robert H.SmithFaculty of AgricultureFood and EnvironmentThe Hebrew University of JerusalemRehovot 76100Israel Department of Animal and Poultry Sciences Virginia TechBlacksburgVA 24061USA

Nutritional stimulation of the developing small intestine of chick embryos can be conducted by in-ovo feeding(IOF).We hypothesized that IOF of glutamine and leucine can enhance small intestinal development by promoting proliferation and differentiation of multipotent small intestinal epithelial cells.Broiler embryos(n=128)were subject to IOF of glutamine(IOF-Gln),leucine(IOF-Leu),NaCl(IOF-NaCl)or no injection(control)at embryonic d 17(E 17).Multipotent,progenitor and differentiated cells were located and quantified in the small intestinal epithelium between E 17 and d 7 after hatch(D 7)in all treatment groups by immunofluorescence of SRY-box transcription factor 9(Sox9)and proliferating cell nuclear antigen(PCNA),in-situ hybridization of leucine-rich repeat containing G-protein coupled receptor 5(Lgr5)and peptide transporter 1(PepT1)and histochemical goblet cell staining.The effects of IOF treatments at E 19(48 h post-IOF),in comparison to control embryos,were as follows:total cell counts increased by 40%,33%and 19%,and multipotent cell counts increased by 52%,50%and 38%,in IOF-Gln,IOF-Leu and IOF-NaCl embryos,respectively.Only IOF-Gln embryos exhibited a significance,36%increase in progenitor cell counts.All IOF treatments shifted Lgr5+ stem cell localizations to villus bottoms.The differentiated,PepT1+region of the villi was 1.9 and 1.3-fold longer in IOF-Gln and IOF-Leu embryos,respectively,while goblet cell densities decreased by 20%in IOF-Gln embryos.Postehatch,crypt and villi epithelial cell counts were significantly higher IOF-Gln chicks,compared to control chicks(Pdifferentiation,resulting in enhanced compartmentalization of multipotent and differentiated cell niches and expansions of the absorptive surface area.

关键词： Chick Intestinal development Proliferation differentiation Multipotent cells In-ovo feeding

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