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Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration Research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina Dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis Laboratory of developmental biology Department of BiologyUniversity of PatrasPatrasGreece Laboratory of cellular and Molecular Neurobiology-Stem Cells Hellenic Pasteur InstituteAthensGreece Department of Physiology School of MedicineUniversity of PatrasPatrasGreece

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the“weaver”mouse,a model of progressive nigrostriatal ***,we extended our investigation in two clinically-relevant ***,we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian ***,we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice,at late stages of *** found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells,marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian *** agreement,we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver ***,the graft strongly induced an endogenous neurogenic response throughout the midbrain,which was significantly enhanced by the administration of microneurotrophin *** results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by ***,the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells(iPSCs) neurotrophic factors Parkinson's disease substantia

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The piRNA size matters

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National Science Review 2024年第2期11卷 96-98页

作者： Jingwen Liu Falong Lu State Key Laboratory of Molecular developmental biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences University of Chinese Academy of Sciences

Small RNAs, including small interfering RNAs(siRNAs), microRNAs(miRNAs) and PIWI-interacting RNAs(piRNAs), serve as pivotal agents in the post-transcriptional regulation of gene expression [1–3]. Among these,piRNAs t... 详细信息

关键词： PIWI

Central cell:the key to determine persistent pollen tube attraction or termination

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Science China(Life Sciences) 2024年第9期67卷 2030-2032页

作者： Jiang-Guo Meng Shi-Zhen Li Hong-Ju Li Center for developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Chongqing Key Laboratory of Plant Resource Conservation and Germplasm Innovation Integrative Science Center of Germplasm Creation Western China(Chongqing)Science CitySchool of Life SciencesSouthwest UniversityChongqing400715 China Key Laboratory of Seed Innovation Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Center for Molecular Agrobiology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Most eukaryotic species depend on sexual reproduction,characterized by fertilization,to produce a new *** process requires the transfer of sperm(male gamete),containing half of the genetic information,from the male to the egg cell(female gamete),which holds half of the maternal genome,within the female reproductive *** strategies have been evolved to ensure fertilization success in plants.

关键词： organs termination holds

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Emerging roles and therapeutic potentials of sphingolipids in pathophysiology:emphasis on fatty acyl heterogeneity

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Journal of Genetics and Genomics 2024年第3期51卷 268-278页

作者： Jinming Mu Sin Man Lam Guanghou Shui State Key Laboratory of Molecular developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100101China Lipidall Technologies Company Limited ChangzhouJiangsu 213000China

Sphingolipids not only exert structural roles in cellular membranes,but also act as signaling molecules in various physiological and pathological processes.A myriad of studies have shown that abnormal levels of sphingolipids and their metabolic enzymes are associated with a variety of human ***,blood sphingolipids can also be used as biomarkers for disease *** review summarizes the biosynthesis,metabolism,and pathological roles of sphingolipids,with emphasis on the biosynthesis of ceramide,the precursor for the biosynthesis of complex sphingolipids with different fatty acyl *** possibility of using sphingolipids for disease prediction,diagnosis,and treatment is also *** endogenous ceramides and complex sphingolipids along with their specific fatty acyl chain to promote future drug development will also be discussed.

关键词： Sphingolipids Ceramide Therapeutic targets Microdomain Biomarker

Non-B-form DNA is associated with centromere stability in newly-formed polyploid wheat

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Science China(Life Sciences) 2024年第7期67卷 1479-1488页

作者： Congyang Yi Qian Liu Yuhong Huang Chang Liu Xianrui Guo Chaolan Fan Kaibiao Zhang Yang Liu Fangpu Han institute of Genetics and developmental biology Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Non-B-form DNA differs from the classic B-DNA double helix structure and plays a crucial regulatory role in replication and ***,the role of non-B-form DNA in centromeres,especially in polyploid wheat,remains ***,we systematically analyzed seven non-B-form DNA motif profiles(A-phased DNA repeat,direct repeat,G-quadruplex,inverted repeat,mirror repeat,short tandem repeat,and Z-DNA)in hexaploid *** found that three of these non-B-form DNA motifs were enriched at centromeric regions,especially at the CENH3-binding sites,suggesting that non-B-form DNA may create a favorable loading environment for the CENH3 *** investigate the dynamics of centromeric non-B form DNA during the alloploidization process,we analyzed DNA secondary structure using CENH3 ChIP-seq data from newly formed allotetraploid wheat and its two diploid *** found that newly formed allotetraploid wheat formed more non-B-form DNA in centromeric regions compared with their parents,suggesting that non-B-form DNA is related to the localization of the centromeric regions in newly formed ***,non-B-form DNA enriched in the centromeric regions was found to preferentially form on young LTR retrotransposons,explaining CENH3's tendency to bind to younger ***,our study describes the landscape of non-B-form DNA in the wheat genome,and sheds light on its potential role in the evolution of polyploid centromeres.

关键词： non-B-form DNA polyploid wheat centromere retrotransposon

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GreenPhos,a universal method for in-depth measurement of plant phosphoproteomes with high quantitative reproducibility

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Molecular Plant 2024年第1期17卷 199-213页

作者： Xiaoxiao Duan Yuanya Zhang Xiahe Huang Xiao Ma Hui Gao Yan Wang Zhen Xiao Chengcheng Huang Zhongshu Wang Bolong Li Wenqiang Yang Yingchun Wang State Key Laboratory of Molecular developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBejing 100101China University of Chinese Academy of Sciences Bejing 100049China Key Laboratory of Photobiology Instute of BotanyChinese Academy of SciencesBejing 100093China

Protein phosphorylation regulates a variety of important cellular and physiological processes in ***-depth profiling of plant phosphoproteomes has been more technically challenging than that of animal *** is largely due to the need to improve protein extraction efficiency from plant cells,which have a dense cell wall,and to minimize sample loss resulting from the stringent sample clean-up steps required for the removal of a large amount of biomolecules interfering with phosphopeptide purification and mass spectrometry *** this end,we developed a method with a streamlined workflow for highly efficient purification of phosphopeptides from tissues of various green organisms including Arabidopsis,rice,tomato,and Chlamydomonas reinhardtii,enabling in-depth identification with high quantitative reproducibility of about 11000 phosphosites,the greatest depth achieved so far with single liquid chromatography-mass spectrometry(LC-MS)runs operated in a data-dependent acquisition(DDA)*** mainstay features of the method are the minimal sample loss achieved through elimination of sample clean-up before protease digestion and of desalting before phosphopeptide enrichment and hence the dramatic increases of time-and *** method,named GreenPhos,combined with single-shot LC-MS,enabled in-depth quantitative identification of Arabidopsis phosphoproteins,including differentially phosphorylated spliceosomal proteins,at multiple time points during salt stress and a number of kinase substrate *** is expected to serve as a universal method for purification of plant phosphopeptides,which,if samples are further fractionated and analyzed by multiple LC-MS runs,could enable measurement of plant phosphoproteomes with an unprecedented depth using a given mass spectrometry technology.

关键词： plant phosphoproteomics phosphopeptides LC–MS Arabidopsis salt stress

Genetic insights into adaptation of alfalfa

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Molecular Plant 2024年第8期17卷 1170-1171页

作者： Yafei Guo Lipeng Kang Fei Lu State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijingChina Key Laboratory of Seed Innovation Institute of Genetics and Developmental BiologyChineseAcademyof SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina CAS-JIC Centre of Excellence for Plant and Microbial Science(CEPAMS) Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijingChina

Climate change is increasingly affecting agricultural outputs,as evidenced by the changing global temperature and extreme weather events that significantly impact crop yields(Lesk et al.,2016).To address this challenge,there is a growing interest in developing crops that can endure these adverse conditions to ensure food *** examples in nature show how crops have adapted to diverse environments(Gutaker and Purugganan,2023),leaving behind a rich genomic *** genomics has started to provide insights into these adaptive processes from evolutionary and genetic perspectives(Savolainen et al.,2013;Aguirre-Liguori et al.,2021;Sang et al.,2022).Recently,Zhang et al.(Zhang et al.,2024)investigated alfalfa(Medicago sativa ***),known as the"queen of forages,"for its broad *** analyzing whole-genome sequencing data of 702 accessions from 24 Medicago species,this study enriches our understanding of how to develop crops and meet the challenges of climate change.

关键词： sativa crops environments

Aagab is required for zebrafish larval development by regulating neural activity

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Journal of Genetics and Genomics 2024年第6期51卷 630-641页

作者： Shihui Ding Tursunjan Aziz Anming Meng Shunji Jia State Key Laboratory of Membrane biology Tsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China Guangzhou Laboratory GuangzhouGuangdong 510320China State Key Laboratory of Molecular developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Clathrin-mediated endocytosis has been implicated in various physiological processes,including nutrient uptake,signal transduction,synaptic vesicle recycling,maintenance of cell polarity,and antigen *** prior knowledge of its importance as a key regulator in promoting clathrin-mediated endocytosis,the physiological function of α-and γ-adaptin binding protein(aagab)remains *** this study,we investigate the biological function of aagab during zebrafish *** establish a loss-of-function mutant of aagab in zebrafish,revealing impaired swimming and early larval *** the high expression level of aagab in the brain,we probe into its physiological role in the nervous *** mutants display subdued calcium responses and local field potential in the optic tectal neurons,aligning with reduced neurotransmitter release(e.g.,norepinephrine)in the tectal neuropil of aagab *** aagab mRNA or nervous stimulant treatment in mutants restores neurotransmitter release,calcium responses,swimming ability,and ***,our observations show delayed release of FM 1-43 in AAGAB knockdown differentiated neuroblastoma cells,pointing towards a probable link to defective clathrin-mediated synaptic vesicle *** conclusion,our study underscores the significance of Aagab in neurobiology and suggests its potential impacts on neurological disorders.

关键词： Aagab Endocytosis Neural activity Synaptic transmitter release Zebrafish

A zebrafish tufm mutant model for the COXPD4 syndrome of aberrant mitochondrial function

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Journal of Genetics and Genomics 2024年第9期51卷 922-933页

作者： Ting Li Tursunjan Aziz Guangyuan Li Lin Zhang Jihua Yao Shunji Jia School of Life Sciences Fudan UniversityShanghai 200438China State Key Laboratory of Membrane biology Tsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China State Key Laboratory of Molecular developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Mitochondrial dysfunction is a critical factor leading to a wide range of clinically heterogeneous and often severe disorders due to its central role in generating cellular *** in the TUFM gene are known to cause combined oxidative phosphorylation deficiency 4(COXPD4),a rare mitochondrial disorder characterized by a comprehensive quantitative deficiency in mitochondrial respiratory chain(MRC)*** development of a reliable animal model for COXPD4 is crucial for elucidating the roles and mechanisms of TUFM in disease pathogenesis and benefiting its medical *** this study,we construct a zebrafish tufm−/−mutant that closely resembles the COXPD4 syndrome,exhibiting compromised mitochondrial protein translation,dysfunctional mitochondria with oxidative phosphorylation defects,and significant metabolic suppression of the tricarboxylic acid *** this COXPD4 zebrafish model,we comprehensively validate the clinical relevance of TUFM mutations and identify probucol as a promising therapeutic approach for managing *** data offer valuable insights for understanding mitochondrial diseases and developing effective treatments.

关键词： Tufm Mitochondria COXPD4 Disease model Zebrafish