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Assessing the efficacy and safety of gemcitabine-induced thrombocytopenia/neutropenia and thrombocytopenia interventions in zebrafish

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Journal of Genetics and Genomics 2024年第9期51卷 970-973页

作者： Jialong Deng Ziyuan Zhou Wangjun Liao Qing Lin yiyue zhang Innovation Centre of Ministry of Education for Development and Diseases School of MedicineSouth China University of TechnologyGuangzhouGuangdong 510006China Department of Hematology The Sixth Affiliated HospitalSchool of MedicineSouth China University of TechnologyFoshanGuangdong 528200China Department of Oncology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China

Cancer is a major global health issue;in 2020,there were 19.29 million new cancer cases and 9.96 million cancer deaths worldwide(Siegel et al.,2023).Despite ongoing research,chemotherapy remains the primary treatment due to its broad anti-cancer effects(Marra and Curigliano,2021).However,intravenous chemotherapeutic drugs commonly induce hematotoxicity,necessitating dose adjustments or treatment ***-induced thrombocytopenia(CIT)and neutropenia(CIN)are the primary manifestations of chemotherapy-induced hematotoxicity,which requires intervention due to the heightened risk of bleeding and infection(Blayney and Schwartzberg,2022).Currently,there are no FDA-approved treatments for CIT(Song and Al-Samkari,2023).While a CIT mouse model using 5-FU has been developed for drug evaluation(Shin et al.,2023),it lacks a comprehensive hematotoxicity assessment and the benefits of high throughput,cost-effectiveness,and ***,it is urgent to develop a high-throughput CIT model for risk assessment and safer chemotherapy strategies with clinical potential.

关键词： chemotherapy treatment visibility

Zebrafish Cdh5 negatively regulates mobilization of aorta-gonad-mesonephros-derived hematopoietic stem cells

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Journal of Genetics and Genomics 2016年第10期43卷 613-616页

作者： Ping Meng Yongxiang Liu Xiaohui Chen Wenqing zhang yiyue zhang Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes Department of Developmental BiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China

Establishment of a hematopoietic stem cell（HSC）pool depends on the appropriate formation,maturation and mobilization of HSCs in *** mice,the aorta-gonad-mesonephros（AGM）is a prominent site for the formation of definitive HSCs from endothelial cells,although the placenta and yolk sac also give rise to HSCs（Mikkola and Orkin,2006;Chen et al.,2009）.After formation,AGM-derived HSCs migrate to the fetal liver（FL）,and ultimately to the bone marrow （BM）, two definitive hematopoietic organs （Cumano and Godin, 2007）.

关键词： AGM HSC Zebrafish Cdh5 negatively regulates mobilization of aorta-gonad-mesonephros-derived hematopoietic stem cells stem

Chemical screening reveals Ronidazole is a superior prodrug to Metronidazole for nitroreductase-induced cell ablation system in zebrafish larvae

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Journal of Genetics and Genomics 2021年第12期48卷 1081-1090页

作者： Siting Lai Ankita Kumari Jixiang Liu yiyue zhang Wenqing zhang Kuangyu Yen Jin Xu Department of Developmental Biology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China Division of Cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou 510006China

The Metronidazole(MTZ)/nitroreductase(NTR)-mediated cell ablation system is the most commonly used chemical-genetic cell ablation method in zebrafish. This system can specifically ablate target cells under spatial and temporal control. The MTZ/NTR system has become a widely used cell ablation system in biological, developmental, and functional studies. However, the inadequate cell-ablation ability of some cell types and the side effects of high concentration MTZ impede extensive applications of the MTZ/NTR system. In the present study, the US drug collection library was searched to extend the NTR system. Six MTZ analogs were found, and the cell-ablation ability of these analogs was tested in zebrafish larvae. The results revealed that two of the NTR substrates, Furazolidone and Ronidazole, ablated target cells more efficiently than MTZ at lower concentrations. Furthermore, the working concentration of Ronidazole, but not Furazolidone and MTZ, did not affect axonal bridge formation during spinal cord regeneration. Our results,taken together, indicate that Ronidazole is a superior prodrug to MTZ for the NTR system, especially for the study of neuron regeneration in zebrafish larvae.

关键词： MTZ Ronidazole NTR Cell ablation Regeneration Zebrafish

The synergistic role of Pu.1 and Fms in zebrafish osteoclast-reducing osteopetrosis and possible therapeutic strategies

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Journal of Genetics and Genomics 2020年第9期47卷 535-546页

作者： Wei Liu Qianqian Di Kailun Li Jing Li Ning Ma Zhibin Huang Jiahao Chen Sheng zhang Wenqing zhang yiyue zhang Division of Cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou510006China Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes Department of Developmental BiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou510515China Department of Orthopedics and Traumatology Nanfang HospitalSouthern Medical UniversityGuangzhou510515China

Osteoclasts are bone resorption cells of myeloid origin. Osteoclast defects can lead to osteopetrosis, a genetic disorder characterized by bone sclerosis for which there is no effective drug treatment. It is known that Pu.1 and Fms are key regulators in myelopoiesis, and their defects in mice can lead to reduced osteoclast numbers and consequent osteopetrosis. Yet how Pu.1 and Fms genetically interact in the development of osteoclasts and the pathogenesis of osteopetrosis is still unclear. Here, we characterized pu.1^(G242) D;fms^(j4e1) double-deficient zebrafish, which exhibited a greater deficiency of functional osteoclasts and displayed more severe osteopetrotic symptoms than the pu.1^(G242) Dor fms^(j4e1) single mutants, suggesting a synergistic function of Pu.1 and Fms in the regulation of osteoclast development. We further demonstrated that Pu.1 plays a dominant role in osteoclastogenesis, whereas Fms plays a dominant role in osteoclast maturation. Importantly, treatment with the drug retinoic acid significantly relieved the different degrees of osteopetrosis symptoms in these models by increasing the number of functional osteoclasts. Thus, we report the development of valuable animal models of osteopetrosis, and our results shed light on drug development for antiosteopetrosis therapy.

关键词： Zebrafish Bone development Osteoclasts Osteopetrosis Therapeutics

Slc20a1b is essential for hematopoietic stem/progenitor cell expansion in zebrafish

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Science China(Life Sciences) 2021年第12期64卷 2186-2201页

作者： Jiakui Chen Gaofei Li Junwei Lian Ning Ma Zhibin Huang Jianchao Li Zilong Wen Wenqing zhang yiyue zhang Department of Developmental Biology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China Division of Cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou 510006China Division of Life Science State Key Laboratory of Molecular NeuroscienceHong Kong University of Science and TechnologyHong KongChina

Hematopoietic stem and progenitor cells(HSPCs)are able to self-renew and can give rise to all blood lineages throughout their lifetime,yet the mechanisms regulating HSPC development have yet to be *** this study,we characterized a hematopoiesis defective zebrafish mutant line named smu07,which was obtained from our previous forward genetic screening,and found the HSPC expansion deficiency in the *** cloning identified that slc20a1b,which encodes a sodium phosphate cotransporter,contributed to the smu07 blood *** analysis demonstrated that mutation of slc20a1b affects HSPC expansion through cell cycle arrest at G2/M phases in a cell-autonomous *** study shows that slc20a1b is a vital regulator for HSPC proliferation in zebrafish early hematopoiesis and provides valuable insights into HSPC development.

关键词： Slc20a1b HSPC zebrafish

Comparative expression analysis of three genes from the Arabidopsis vacuolar Na^+/H^+ antiporter (AtNHX) family in relation to abiotic stresses

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Chinese Science Bulletin 2007年第13期52卷 1754-1763页

作者： WANG WeiQuan LI Yin zhang yiyue YANG CuiPing ZHENG NuoYan XIE Qi State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-sen University Guangzhou 510275 China State Key Laboratory of Plant Genomics Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101 China

Na^+/H^+ antiporters (NHX) are ubiquitous transmembrane proteins that play a key role in salt tolerance of plants. In this study, the sequence of 3 Arabidopsis NHX gene (AtNHX2―4) were compared with other AtNHX members. Putative cis-elements analysis identified elements that have been associated with stress responses. The activities of the promoters AtNHX2―4 were studied in transgenic plants carrying corresponding promoter-β-glucuronidase (GUS) fusions. The AtNHX2 promoter-GUS analysis indicated that AtNHX2 was expressed in constitutive pattern with high GUS activity in roots and leaves. AtNHX2 promoter activity was not up-regulated by NaCl or abscisic acid (ABA), in contrast to the AtNHX1 promoter which was previously studied. The AtNHX3 and AtNHX4 promoters showed tissue-specific activities. Strong GUS activity was detected in roots and vascular bundles of the stele in plants carry-ing an AtNHX4 promoter-GUS fusion, and GUS activity increased under salt stress suggesting a func-tion related to salt tolerance. Transgenic plants carrying the AtNHX3 promoter-GUS fusion showed strong GUS activity in petals, stamens and tops of siliques, suggesting a possible role of AtNHX3 in flower and seed development. Results of histochemical analysis suggested that AtNHX2―4 are involved in divergent functions and are differentially regulated under abiotic stress. The structure of AtNHX4 was predicted to include 12 transmembrane regions and a NHX domain. Overexpression of AtNHX4 in Arabidopsis transgenic lines confers greater salt tolerance than in wild type plants. These results suggest that AtNHX4 may encode a putative vacuolar NHX that plays an important role in salt tolerance.

关键词：生物应力耐盐性阿布属植物基因研究

Comparison Analysis of Transcripts from the Halophyte Thellungiella halophila

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Journal of Integrative Plant Biology 2008年第10期50卷 1327-1335页

作者： yiyue zhang Jianbin Lai Shouhong Sun Yin Li Yuanyuan Liu Liming Liang Mingsheng Chen Qi Xie State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-sen University Guangzhou 510275 China State Key Laboratory of Plant Genomics National Centre for Plant Gene Research Institute of Genetics and Developmental Biology the Chinese Academy of Sciences Beijing 100101 China

The Brassicaceae family halophyte Thellungiella halophila has a high salinity tolerance and serves as a valuable halophytic genetic model plant with experimental convenience similar to Arabidopsis thaliana. A cDNA library of Thellungiella was generated from salt-treated seedlings including rosettes and roots. More than 1000 randomly selected clones were sequenced and 946 expressed sequence tags （ESTs） were generated. The accession numbers of our EST data are available online in the GenBank database from EC598928 to EC599965. In total 679 unique clusters were assembled, and 632 （93%） had BLASTX hits in the nr databases and 7% are Thellungiella unique. According to the Gene Ontology （GO） hierarchy, 385 of 679 unigenes were categorized. Compared with public Arabidopsis microarray data, our results provide more potential salt tolerance genes in Thellungiella. These results will provide a broader coverage into Thellungiella transcriptome and benefit the discovery of salt tolerance related genes.

关键词： expressed sequence tag gene ontology salt tolerance Thellungiella transcripts.

Segmental Translocation Contributed to the Origin of the Brassica S-locus

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Horticultural Plant Journal 2020年第3期6卷 167-178页

作者： Yinan Cui Mu Zhuang Jian Wu Jisheng Liu yiyue zhang Lingkui zhang Yile Huang Xu Cai Jianli Liang Kang zhang Xiaowu Wang Feng Cheng Institute of Vegetables and Flowers Chinese Academy of Agricultural SciencesKey Laboratory of Biology and Genetic Improvement of Horticultural Crops of the Ministry of AgricultureSino-Dutch Joint Laboratory of Horticultural GenomicsBeijing 100081China

Self-incompatibility(SI),which has recurred during the evolution of plants,is one of the most important cross-pollination mating *** S-loci have been reported in Brassicaceae,namely,Arabidopsis lyrata(Al),Brassica(Br),and Leavenworthia alabamica(La)***,through multi-genomic comparative analysis of 20 species,we revealed that the most ancient S-locus was formed prior to the divergence of Brassicaceae lineage I and *** retained and inherited by Arabidopsis,as the Al S-locus in Brassicaceae lineage ***,we found that the Br S-locus,which has been widely used in the breeding of Brassica crops to generate hybrid seeds,was formed through segmental translocation(ST)in the hexaploid ancestor of Brassica in Brassicaceae lineage *** Br S-locus was evolved through a ST from one of the triplicated ancestral S-locus paralogs in the Brassica hexaploidy ancestor,while the other two S-locus paralogs were *** with the previous discovery that the La S-locus was formed through a secondary origin in Brassicaceae lineage I,we conclude the monophyletic origin of Al and Br S-loci and clarify the evolutionary route of S-loci in the Brassicaceae *** findings will contribute to evolutionary studies and breeding applications of the S-locus in Brassicaceae.

关键词： Self incompatibility SRK,SCR Gene evolution Brassicaceae

Large-Scale Forward Genetic Screening Analysis of Development of Hematopoiesis in Zebrafish

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Journal of Genetics and Genomics 2012年第9期39卷 473-480页

作者： Kun Wang Zhibin Huang Lingfeng Zhao Wei Liu Xiaohui Chen Ping Meng Qing Lin Yali Chi Mengchang Xu Ning Ma yiyue zhang Wenqing zhang Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes Department of Cell Biology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China

Zebrafish is a powerful model for the investigation of *** order to isolate novel mutants with hematopoietic defects, large-scale mutagenesis screening of zebrafish was *** scoring specific hematopoietic markers,52 mutants were identified and then classified into four types based on specific phenotypic *** mutant represented a putative mutation of a gene regulating the relevant aspect of hematopoiesis,including early macrophage development,early granulopoiesis,embryonic myelopoiesis,and definitive erythropoiesis/*** method should be applicable for other types of genetic screening in *** addition,further study of the mutants we identified may help to unveil the molecular basis of hematopoiesis.

关键词： Zebrafish Large-scale screening Hematopoiesis