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Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis

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Zoological Research 2024年第3期45卷 617-632页

作者： Jing-Hang Jiang Yi-Fu Wang Jie Zheng Yi-Ming Lei Zhong-Yuan Chen Yi Guo Ya-Jie Guo Bing-Qian Guo Yu-Fang Lv Hong-Hong Wang Juan-Juan Xie Yi-Xuan Liu Ting-Wei Jin Bi-Qi Li Xiao-Shu Zhu Yong-Hua Jiang Zeng-Nan Mo Center for Genomic and Personalized Medicine Guangxi Collaborative Innovation Center for Genomic and Personalized MedicineGuangxi Key Laboratory for Genomic and Personalized MedicineGuangxi Medical UniversityNanningGuangxi 530021China Department of Urology First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530021China Reproductive Medicine Center Jingmen People’s HospitalJingChu University of Technology Affiliated Central HospitalJingmenHubei 448000China School of Computer Science and Engineering Yulin Normal UniversityYulinGuangxi 537000China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanningGuangxi 530021China Department of Pathology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China Department of Obstetrics and Gynecology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China

The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://***:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

关键词： Tree shrew Adrenal gland Dehydroepiandrosterone Genome-wide association studies disease model

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Echocardiographic Evaluation of Coronary Abnormalities and Cardiac Function in a Murine model of Kawasaki disease Using High-frequency Ultrasound

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Chinese Medical Journal 2017年第12期130卷 1467-1474页

作者： Xin-Xin Zhang Zhong-Dong Du Shang-GuanWen Xiu-Ping Sun Department of Cardiology Beijing Children's Hospital Capital Medical University Beijing 100045 China Key Laboratory of Major disease in Children Ministry of Health Beijing 100045 China pediatric Cardiac Intensive Center Beijing Anzhen Hospital Capital Medical University Beijing 100029 China Chinese Academy of Medical Sciences and Comparative Medical Center Beijing 100021 China

Background： Murine model of coronary arterial inflammation has been widely accepted as an animal model of and used in Kawasaki disease （KD）. This study sought to evaluate the developmental changes of coronary arteries and cardiac function in a murine model of KD with a high-frequency ultrasound system and to provide evidence for the preparation of the model of KD. Methods： Lactobacillus case~ cell wall extract was prepared and injected into C57BL/6 mice intraperitoneally （i.p.） to induce KD. A total of 120 mice were grouped into three groups. The intravenous immunoglobulin （IVIG） treatment group was i.p. injected with IVIG （2 g/kg）, while the KD model and normal control groups were i.p. injected with 0.5 ml of phosphate buffered solution on day 5. All high-resolution echocardiography detection of mouse heart was performed by the same senior technician. Animal echocardiography was performed by measuring the coronary artery dimensions and cardiac function on days 0, 7, 14, 28, and 56 （high-resolution small animal ultrasound [Vevo770 pattem; VisualSonic, Canada] with broadband probe [RMVTM707B; frequency, 30 mHz; depth of focus, 1.2 cm]） which were measured and analyzed with Vevo770 software. Results： Pathological studies revealed focal inflammatory infiltrate asymmetrically distributed around the coronary artery trunk in the KD model group. Echocardiographic study including coronary dimension and cardiac function measurements was successfully performed in all subjects. The KD model and IVIG treatment groups showed left coronary artery dilation on days 7, 14, 28, and 56. The diameter of left coronary artery in the KD model group （0.53 ± 0.09 mm; 0.36 ± 0.07 mm; 0.34 ±0.05 mm; 0.34±0.04 mm） was significantly larger than those of 1VIG treatment group （0.22± 0.02 mm; 0.28 ± 0.03 mm; 0.26± 0.03 mm; 0.27 ±0.05 mm; 0.26 ± 0.03 mm; all P〈 0.01） and the normal control group （0.21 ±0.02 mm; 0.22 ±0.03 mm; 0.22± 0.02 mm; 0.23 ± 0.02 mm; 0.27± 0.04 mm; all P 〈 0.01） on days 7, 14, 28, and 56. No significant differences were ob

关键词： disease model Echocardiography Kawasaki disease Murine

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Islet organoid as a promising model for diabetes

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Protein & Cell 2022年第4期13卷 239-257页

作者： Xiaofei Zhang Zhuo Ma Eli Song Tao Xu National Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China Key Laboratory of Molecular Biophysics of the Ministry of Education College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China Guangzhou Regenerative Medicine and Health Guangdong Laboratory(Bioland Laboratory) Guangzhou 510005China

Studies on diabetes have long been hampered by a lack of authentic disease models that,ideally,should be unlimited and able to recapitulate the abnormalities involved in the development,structure,and function of human pancreatic islets under pathological conditions.Stem cell-based islet organoids faithfully recapitulate islet development in vitro and provide large amounts of three-dimensional functional islet biomimetic materials with a morphological structure and cellular composition similar to those of native islets.Thus,islet organoids hold great promise for modeling islet development and function,deciphering the mechanisms underlying the onset of diabetes,providing an in vitro human organ model for infection of viruses such as SARS-CoV-2,and contributing to drug screening and autologous islet transplantation.However,the currently established islet organoids are generally immature compared with native islets,and further efforts should be made to improve the heterogeneity and functionality of islet organoids,making it an authentic and informative disease model for diabetes.Here,we review the advances and challenges in the generation of islet organoids,focusing on human pluripotent stem cell-derived islet organoids,and the potential applications of islet organoids as disease models and regenerative therapies for diabetes.

关键词： islet organoid diabetes pluripotent/adult stem cell pancreaticβcell disease model

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Base editors:development and applications in biomedicine

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Frontiers of Medicine 2023年第3期17卷 359-387页

作者： Yanhui Liang Fangbing Chen Kepin Wang Liangxue Lai China-New Zealand Joint Laboratory on Biomedicine and Health CAS Key Laboratory of Regenerative BiologyGuangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineCentre for Regenerative Medicine and HealthHong Kong Institute of Science and InnovationGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Research Unit of Generation of Large Animal disease models Chinese Academy of Medical Sciences(2019RU015)Guangzhou 510530China Sanya Institute of Swine Resource Hainan Provincial Research Centre of Laboratory AnimalsSanya 572000China Guangdong Provincial Key Laboratory of Large Animal models for Biomedicine Wuyi UniversityJiangmen 529020China

Base editor(BE)is a gene-editing tool developed by combining the CRISPR/Cas system with an individual deaminase,enabling precise single-base substitution in DNA or RNA without generating a DNA double-strand break(DSB)or requiring donor DNA templates in living cells.Base editors offer more precise and secure genome-editing effects than other conventional artificial nuclease systems,such as CRISPR/Cas9,as the DSB induced by Cas9 will cause severe damage to the genome.Thus,base editors have important applications in the field of biomedicine,including gene function investigation,directed protein evolution,genetic lineage tracing,disease modeling,and gene therapy.Since the development of the two main base editors,cytosine base editors(CBEs)and adenine base editors(ABEs),scientists have developed more than 100 optimized base editors with improved editing efficiency,precision,specificity,targeting scope,and capacity to be delivered in vivo,greatly enhancing their application potential in biomedicine.Here,we review the recent development of base editors,summarize their applications in the biomedical field,and discuss future perspectives and challenges for therapeutic applications.

关键词： base editing CBE ABE ADAR DdCBE disease model therapeutic application

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Genome Editing and Its Applications in model Organisms

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Genomics, Proteomics & Bioinformatics 2015年第6期13卷 336-344页

作者： Dongyuan Ma Feng Liu State Key Laboratory of Membrane Biology Institute of Zoology Chinese Academy of Sciences

Technological advances are important for innovative biological research. Development of molecular tools for DNA manipulation, such as zinc finger nucleases （ZFNs）, transcription activator-like effector nucleases （TALENs）, and the clustered regularly-interspaced short palin- dromic repeat （CR1SPR）/CRISPR-associated （Cas）, has revolutionized genome editing. These approaches can be used to develop potential therapeutic strategies to effectively treat heritable dis- eases. In the last few years, substantial progress has been made in CRISPR/Cas technology, includ- ing technical improvements and wide application in many model systems. This review describes recent advancements in gennme editing with a particular focus on CRISPR/Cas, covering the under- lying principles, technological optimization, and its application in zehrafish and other model organ- isms, disease modeling, and gene therapy used for personalized medicine.

关键词： Genome editingCRISPR/Cas Zebrafish disease model Gene therapy

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Zebrafish as a model for Human Ciliopathies

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Journal of Genetics and Genomics 2016年第3期43卷 107-120页

作者： Zhu Song Xiaoli Zhang Shuo Jia Pamela C.Yelick Chengtian Zhao Institute of Evolution & Marine Biodiversity College of Marine Life Science Ocean University of China Department of Orthodontics Division of Craniofacial and Molecular Genetics Tufts University Laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and Technology

Cilia, microtubule-based structures found on the surface of almost all vertebrate cells, play an array of diverse biological functions. Abnormal ciliary axonemal structure and function can result in a class of genetic disorders that are collectively termed ciliopathies. model organisms, including Chlamydomonas reinhardtii and Caenorhabditis elegans have been widely used to study the complex genetic basis of ciliopathies. Here, we review the advantages of the zebrafish as a vertebrate model for human ciliopathies. We summarize the features of zebrafish cilia, and the major findings and contributions of the zebrafish model in recent studies of human ciliopathies. We also discuss the new genome editing approaches being efficiently used in zebrafish, and the exciting prospects of these approaches in modeling human ciliopathies.

关键词： Cilia Zebrafish Ciliopathy disease model

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Study of Candida Albicans Vaginitis model in Kunming Mice

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2007年第3期27卷 307-310页

作者：陈琢孔小锋 Department of Integrated Traditional Chinese Medicine and Western Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

The model of vaginal candidiasis in Kunming mice was constructed in order to search for the optima construction conditions and provide an economic animal model of Candida albicans (C. albicans) vaginitis. Estrogen benzoate (E2) was given to mice at different concentrations ranging from 0.0 to 0.05 mg/mouse (4 levels) beginning 72 h prior to vaginal inoculation, then mice were in- oculated intravaginally with various concentrations of stationary-phase C. albicans blastoconidia (ATCC90028) (5 levels) in 20 μL of phosphate-buffered saline (PBS) in each E2 level. General state, scores of genital pathology, the hyphae and vaginal fungal burden (CFU) in vaginal lavage fluid, the hydrops rate of uterus and vaginal tissues for pathological section in mice were observed and ob- tained at day 2, 4, 7, 14 and 21 after inoculation. The results showed the infection rate in mice was related to the dosage of E2 and concentration of C. albicans blastoconidia. Additionally there was better cross-effect between the two treated factors. The infection rate was about 80% on the day 4, and could reach 100% on the day 7 until the end of experiment after inoculated intravaginally in groups of E2I3, E2 0.025 mg/mouse injected hypodermically and inoculated intravaginally with 5×104 C. albicans blastoconidia, and large amount of hyphae and blastoconidia could be observe in superfi- cial layer tissue and canal of vaginal by PAS. From the results in our experiment it was concluded that E2I3 was the optima construction condition in kunming mice.

关键词： Candida albicans vulvovaginal disease model Mice hyphae

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Influence of species,age and weight on the establishment of a murine model of brachial plexus root avulsion

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Neural Regeneration Research 2010年第10期5卷 764-768页

作者： Lifeng Yan Xiuchun Zhao Yaqiong Wang Lin Wang Xiao Cheng Lihua Zhou Xia Feng Department of Human Anatomy Zhongshan School of Medicine Sun Yat-sen University Guangzhou 510080 Guangdong Province China Department of Anesthesiology First Affiliated Hospital of Sun Yat-sen University Guangzhou 510080 Guangdong Province China

BACKGROUND： Animal models of brachial plexus root avulsion are required for the study of brachial plexus root injuries. The established ventral approach results in slight injuries, and is similar to mechanisms underlying human brachial plexus root avulsion.OBJECTIVE： To analyze the effects of weight, age, and species on the success rate of brachial plexus root avulsion, and to determine the perfect method for establishing models of brachial plexus root avulsion.DESIGN, TIME AND SETTING： A randomized, block design was performed at the Laboratory of Professor Lihua Zhou, Zhongshan School of Medicine, Sun Yat-sen University, China from June 2008 to June 2009.MATERIALS： Sprague Dawley （SD） rats, golden hamsters, and BALb/C mice were used in the present study.METHODS： All animals were randomly subjected to classical brachial plexus root avulsion and modified brachial plexus root avulsion.MAIN OUTCOME MEASURES： Success rate of brachial plexus root avulsion. RESULTS： The success rate of brachial plexus root avulsion was greater in the modified group than in the classical group （P〈0.01）. Moreover, the difference was significant in 15-day-old SD rats, 5-week-old SD rats, and 3-month-old BALb/C mice （P〈0.01）. The success rate of brachial plexus root avulsion was greater in the same weight, 15-day-old juvenile SD rats, than in the 3-month-old BALb/C mice （classical group, P〈0.01; modified group, P〈0.05）. The success rate of brachial plexus root avulsion was significantly greater in 3-month-old golden hamsters than in 5-week-old SD rats in the classical group （P〈0.05）. The success rate of brachial plexus root avulsion was significantly lower in the 15-day-old SD rats compared with the 5-week-old and 3-month-old SD rats in the classical group （P〈0.01）. However, there was no significant difference in the success rate of brachial plexus root avulsion between various ages of SD rats in the modified group （P〉0.05）.CONCLUSION： Modified surgery to induce brachial plexus root avulsion significantly increases the success rate of mode

关键词： brachial plexus root injury species age animal disease model modified surgery peripheral nerve injury neural regeneration

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Establishment of an animal model of dural venous sinus embolism

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Neural Regeneration Research 2008年第5期3卷 561-564页

作者： Peixian Zhang Chongzhi Zhang Yi Qin Quanrui Ma Jianying Du Ying Cai Department of Anatomy Tianjin Medical University Tianjin 300070 China Department of Anatomy Ningxia Medical College Yinchuan 750004 Ningxia Hui Autonomous Region China

BACKGROUND： The pathological mechanism of secondary brain lesion following an embolism remains unclear. The establishment of an animal model that imitates the clinical pathophysiological processes is crucial to better study this disease during a certain time window. OBJECTIVE： To establish a new animal model of dural venous sinus embolism that is simple, has a high success rate, and emulates the pathophysiological course of clinical disease. DESIGN, TIME AND SETTING： A randomized block design trial was performed at the Department of Anatomy, Ningxia Medical College between March and December 2007. MATERIALS： Fifty-eight healthy, adult, Sprague Dawley rats were used in the present study. Plastic emboli, with a total length of 0.4 cm, were self-made. Each plastic embolus had a conical anterior segment; the largest diameter being 0.12 cm. The posterior segment became gradually thin and flat, with a width of 0.2 cm and length of 0.1 cm. METHODS： The fifty-eight rats were randomly divided into three groups： control （n = 6）, embolism （n = 26）, and sham-embolism （n = 26） groups. In the embolism group, a solid embolus was slowly inserted and fixed into the posterior part of the superior sagittal sinus against the flow of blood. The posterior segment was detained outside the superior sagittal sinus for fixing. In the sham-embolism group, rats were subjected only to sinus sagittalis superior exposure. In the control group, rats received no treatments. In both the embolism and the sham-embolism groups, the rat brains were resected at 6 hours, 1, 3, and 5 days post-surgery. MAIN OUTCOME MEASURES：（1） Brain surface appearance in the embolism and sham-embolism groups. （2） Thrombosis in the embolism group. （3） Cerebrospinal fluid content in the above-mentioned two groups. RESULTS： In the embolism group, the model success rate was 92% （24/26）. There was visible thrombosis in the superior sagittal sinus. Cerebral edema was noticeable under a microscope. These changes were visible at 6 hours after embolism and were most obvious at

关键词： dural venous sinus embolism disease model rats

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EVALUATION ON FACTORS INFLUENCING LIVER CANCER METASTASIS AFTER LIVER SURGERY BY A MOUSE model

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Chinese Journal of Cancer Research 1999年第2期11卷 101-104页

作者：白莉黄志强黄洁王燕生 Laboratory of Hepatobiliary diseases Department of General Surgery PLA General Hospital Beijing China

Objective: To evaluate the influence of surgical trauma on liver cancer metastasis. Methods: A mouse model of experimental liver cancer metastasis was established by subcapsule injecting hepatoma ascites tumor cells (H22) into spleen of NIH mice. Simple intrasplenic inoculation, with sham operation, partial hepatectomy, total occlusion of hepatic blood inflow and blood loss and re-perfusion were performed and metastatic effects were observed. Results: There were significant higher metastasis-augmenting effects in sham operation and partial hepatectomy groups. Compared with no-blood transfusion, blood transfusion group was found to be potent to increase intrahepatic metastases. But, neither inhibition nor enhancement with total occlusion of hepatic blood inflow for 20 and 30 minutes was seen. Conclusions: Surgical trauma, especially partial hepatectomy and blood transfusion, are involved in enhancing metastasis, but total occlusion of hepatic blood inflow is not responsible for enhanced liver metastasis in the experimental metastasis model.

关键词： Primary hepatocellular carcinoma Liver metastasis disease model Hepatectomy Surgical trauma Blood transfusion Mice

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