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Complete canine spinal cord transection model: a large animal model for the translational research of spinal cord regeneration

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Science China(Life Sciences) 2018年第1期61卷 115-117页

作者： Sufang Han Xing Li Zhifeng Xiao Jianwu Dai State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences

Traumatic spinal cord injury (SCI) usually results in devastating neurologic deficits and disability. In the United states,approximately 12,500 new cases are reported each year, while an estimated 100,000–140,000 new cases occur every year in China (National Spinal Cord Injury Statistical Center, 2016).Spinal cord injuries are highly disabling and primarily affect young adults, and therefore create great psychological and financial burden on the affected individuals and their families.

关键词：动物模型绳索翻译新生犬损害成年人案例

RLKs orchestrate the signaling in plant male-female interaction

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Science China(Life Sciences) 2016年第9期59卷 867-877页

作者： Hongju Li Wei-Cai Yang State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences

Different from animals, sessile plants are equipped with a large receptor-like kinase(RLK) superfamily. RLKs are a family of single trans-membrane proteins with divergent N-terminal extracellular domains capped by a signal peptide and C-terminal intracellular kinase. Researches in the last two decades have uncovered an increasing number of RLKs that regulate plant development, stress response and sexual reproduction, highlighting a dominant role of RLK signaling in cell-to-cell communications. Sexual reproduction in flowering plants is featured by interactions between the male gametophyte and the female tissues to facilitate sperm delivery and fertilization. Emerging evidences suggest that RLKs regulate almost every aspect of plant reproductive process, especially during pollination. Therefore, in this review we will focus mainly on the function and signaling of RLKs in plant male-female interaction and discuss the future prospects on these topics.

关键词：开花植物信号肽类受体激酶类受体蛋白激酶编排有性生殖胞外结构域跨膜蛋白

Phosphatidylcholine deficiency increases ferroptosis susceptibility in the Caenorhabditis elegans germline

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Journal of Genetics and Genomics 2023年第5期50卷 318-329页

作者： Jinglin Zhu Wei Meng Sin Man Lam Guanghou Shui Xun Huang State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Ferroptosis,a regulated and iron-dependent form of cell death characterized by peroxidation of membrane phospholipids,has tremendous potential for the therapy of human diseases.The causal link between phospholipid homeostasis and ferroptosis is incompletely understood.Here,we reveal that spin-4,a previously identified regulator of the“B12-one-carbon cycle-phosphatidylcholine(PC)”pathway,sustains germline development and fertility by ensuring PC sufficiency in the nematode Caenorhabditis elegans.Mechanistically,SPIN-4 regulates lysosomal activity which is required for B12-associated PC synthesis.PC deficiency-induced sterility can be rescued by reducing the levels of polyunsaturated fatty acids,reactive oxygen species,and redox-active iron,which indicates that the sterility is mediated by germline ferroptosis.These results highlight the critical role of PC homeostasis in ferroptosis susceptibility and offer a new target for pharmacological approaches.

关键词： Phosphatidylcholine Ferroptosis SPIN-4 Sterility Lysosome

Lineage tracing reveals the origin of Nestin-positive cells are heterogeneous and rarely from ependymal cells after spinal cord injury

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Science China(Life Sciences) 2022年第4期65卷 757-769页

作者： Xiaoyu Xue Muya Shu Zhifeng Xiao Yannan Zhao Xing Li Haipeng Zhang Yongheng Fan Xianming Wu Bing Chen Bai Xu Yaming Yang Weiyuan Liu Sumei Liu Jianwu Dai State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100190China University of Chinese Academy of Sciences Beijing100190China

Nestin is expressed extensively in neural stem/progenitor cells during neural development, but its expression is mainly restricted to the ependymal cells in the adult spinal cord. After spinal cord injury(SCI), Nestin expression is reactivated and Nestinpositive(Nestin;) cells aggregate at the injury site. However, the derivation of Nestin;cells is not clearly defined. Here, we found that Nestin expression was substantially increased in the lesion edge and lesion core after SCI. Using a tamoxifen inducible CreER(T2)-loxP system, we verified that ependymal cells contribute few Nestin;cells either to the lesion core or the lesion edge after SCI. In the lesion edge, GFAP+astrocytes were the main cell type that expressed Nestin;they then formed an astrocyte scar.In the lesion core, Nestin;cells expressed αSMA or Desmin, indicating that they might be derived from pericytes. Our results reveal that Nestin;cells in the lesion core and edge came from various cell types and rarely from ependymal cells after complete transected SCI, which may provide new insights into SCI repair.

关键词： Nestin ependymal cells spinal cord injury astrocytes pericytes

Endocrine function of pheromones couples fat rationing and nutrient scarcity

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Science China(Life Sciences) 2022年第6期65卷 1267-1269页

作者： Jinglin Zhu Xun Huang State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Harsh environmental conditions, such as food scarcity,drought and coldness, are ubiquitous threats to most living things. During evolution, organisms have developed diverse strategies to survive such inhospitable peri... 详细信息

关键词： Olsen ration drought

Drosophila homolog of the intellectual disability-related long-chain acyl-CoA synthetase 4 is required for neuroblast proliferation

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Journal of Genetics and Genomics 2019年第1期46卷 5-17页

作者： Mingyue Jia Danqing Meng Mo Chen Tingting Li Yong Q.Zhang Aiyu Yao State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences University of Chinese Academy of Sciences

Mutations in long-chain acyl-CoA synthetase 4 (ACSL4) are associated with non-syndromic X-linked intellectual disability (ID). However, the neural functions of ACSL4 and how loss of ACSL4 leads to ID remain largely unexplored. We report here that mutations in Acsl, the Drosophila ortholog of human ACSL3 and ACSL4, result in developmental defects of the mushroom body (MB), the center of olfactory learning and memory. Specifically, Acsl mutants show fewer MB neuroblasts (Nbs) due to reduced proliferation activity and premature differentiation. Consistently, these surviving Nbs show reduced expression of cyclin E, a key regulator of the G1-to S-phase cell cycle transition, and nuclear mislocalization of the transcriptional factor Prospero, which is known to repress self-renewal genes and activate differentiating genes. Furthermore, RNA-seq analysis reveals downregulated Nb-and cell-cyclerelated genes and upregulated neuronal differentiation genes in Acsl mutant Nbs. As Drosophila Acsl and human ACSL4 are functionally conserved, our findings provide novel insights into a critical and previously unappreciated role of Acsl in neurogenesis and the pathogenesis of ACSL4-related ID.

关键词： ACSL4 Drosophila Mushroom body Neuroblast Neural stem cell Premature differentiation

PRMT5 determines the pattern of polyploidization and prevents liver from cirrhosis and carcinogenesis

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Journal of Genetics and Genomics 2023年第2期50卷 87-98页

作者： Jincheng Wang Xiang Huang Daoshan Zheng Qiuling Li Mei Mei Shilai Bao State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China School of Life Sciences University of Chinese Academy of SciencesBeijing 100049China

Human hepatocellular carcinoma(HCC)occurs almost exclusively in cirrhotic livers.Here,we report that hepatic loss of protein arginine methyltransferase 5(PRMT5)in mice is sufficient to cause cirrhosis and HCC in a clinically relevant way.Furthermore,pathological polyploidization induced by hepatic loss of PRMT5 promotes liver cirrhosis and hepatic tumorigenesis in aged liver.The loss of PRMT5 leads to hyperaccumulation of P21 and endoreplication-dependent formation of pathological mono-nuclear polyploid hepatocytes.PRMT5 and symmetric dimethylation at histone H4 arginine 3(H4R3me2s)directly associate with chromatin of P21 to suppress its transcription.More importantly,loss of P21 rescues the pathological mono-nuclear polyploidy and prevents PRMT5-deficiency-induced liver cirrhosis and HCC.Thus,our results indicate that PRMT5-mediated symmetric dimethylation at histone H4 arginine 3(H4R3me2s)is crucial for preventing pathological polyploidization,liver cirrhosis and tumorigenesis in mouse liver.

关键词： Pathological polyploidizaion Hepatocellular carcinoma Cirrhosis PRMT5 Aging

Lipidomics as a Principal Tool for Advancing Biomedical Research

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Journal of Genetics and Genomics 2013年第8期40卷 375-390页

作者： Sin Man Lam Guanghou Shui State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of Sciences

Lipidomics, which targets at the construction of a comprehensive map of lipidome comprising the entire lipid pool within a cell or tissue, is currently emerging as an independent discipline at the interface of lipid biology, technology and medicine. The diversity and complexity of the biological lipidomes call for technical innovation and improvement to meet the needs of various biomedical studies. The recent wave of expansion in the field of lipidomic research is mainly attributed to advances in analytical technologies, in particular, the development of new mass spectrometric and chromatographic tools for the characterization and quantification of the wide array of diverse lipid species in the cellular lipidome. Here, we review some of the key technical advances in lipidome analysis and put forth the applications of lipidomics in addressing the biological roles of lipids in numerous disease models including the metabolic syndrome, neurodegenerative diseases and infectious diseases, as well as the increasing urgency to construct the lipidome inventory for various mammalian/organism models useful for biomedical research.

关键词： Lipidomics Mass spectrometry Metabolic syndrome Neurodegenerative diseases Infectious diseases

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 plants.In-depth profiling of plant phosphoproteomes has been more technically challenging than that of animal phosphoproteomes.This 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 analysis.To 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)mode.The 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 cost-effectiveness.The 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 motifs.GreenPhos 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