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| 1 | Generation of rat blood vasculature and hematopoietic cells in rat-mouse chimeras by blastocyst complementation显示文摘Interspecies chimera through blastocyst complementation could be an alternative approach to create human organs in animals by using human pluripotent stem cells.A mismatch of the major histocompatibility complex of vascular endothelial cells between the human and host animal will cause graft rejection in the transplanted organs.Therefore,to achieve a transplantable organ in animals without rejection,creation of vascular endothelial cells derived from humans within the organ is necessary.In this study,to explore whether donor xeno-pluripotent stem cells can compensate for blood vasculature in host animals,we generated rat-mouse chimeras by injection of rat embryonic stem cells(rESCs)into mouse blastocysts with deficiency of Flk-1 protein,which is associated with endothelial and hematopoietic cell development.We found that rESCs could differentiate into vascular endothelial and hematopoietic cells in the rat-mouse chimeras.The whole yolk sac(YS)of Flk-1^EGFP/ECFP rat-mouse chimera was full of rat blood vasculature.Rat genes related to vascular endothelial cells,arteries,and veins,blood vessels formation process,as well as hematopoietic cells,were highly expressed in the YS.Our results suggested that rat vascular endothelial cells could undergo proliferation,migration,and self-assembly to form blood vasculature and that hematopoietic cells could differentiate into B cells,T cells,and myeloid cells in rat-mouse chimeras,which was able to rescue early embryonic lethality caused by Flk-1 deficiency in mouse. | Xiaomin Wang Hui Shi Juanjuan Zhou Qingjian Zou Quanjun Zhang Shixue Gou Pengfei Chen Lisha Mou Nana Fan Yangyang Suo Zhen Ouyang Chengdan Lai Quanmei Yan Liangxue Lai | 2020 | Journal of Genetics and Genomics2020，47，5： | 2 |
| 2 | Double knock-in pig models with elements of binary Tet-On and phiC31 integrase systems for controllable and switchable gene expression显示文摘Inducible expression systems are indispensable for precise regulation and in-depth analysis of biological process.Binary Tet-On system has been widely employed to regulate transgenic expression by doxycycline.Previous pig models with tetracycline regulatory elements were generated through random integration.This process often resulted in uncertain expression and unpredictable phenotypes,thus hindering their applications.Here,by precise knock-in of binary Tet-On 3G elements into Rosa26 and Hipp11 locus,respectively,a double knock-in reporter pig model was generated.We characterized excellent properties of this system for controllable transgenic expression both in vitro and in vivo.Two att P sites were arranged to flank the td Tomato to switch reporter gene.Single or multiple gene replacement was efficiently and faithfully achieved in fetal fibroblasts and nuclear transfer embryos.To display the flexible application of this system,we generated a pig strain with Dox-inducing h KRASexpression through phiC31 integrase-mediated cassette exchange.After eight months of Dox administration,squamous cell carcinoma developed in the nose,mouth,and scrotum,which indicated this pig strain could serve as an ideal large animal model to study tumorigenesis.Overall,the established pig models with controllable and switchable transgene expression system will provide a facilitating platform for transgenic and biomedical research. | Qin Jin Xiaoyu Yang Shixue Gou Xiaoyi Liu Zhenpeng Zhuang Yanhui Liang Hui Shi Jiayuan Huang Han Wu Yu Zhao Zhen Ouyang Quanjun Zhang Zhaoming Liu Fangbing Chen Weikai Ge Jingke Xie Nan Li Chengdan Lai Xiaozhu Zhao Jiaowei Wang Meng Lian Lei Li Longquan Quan Yinghua Ye Liangxue Lai Kepin Wang | 2022 | Science China(Life Sciences)2022，65，11： | 1 |
| 3 | Generation of pigs with humanized type Ⅱ collagen by precise human COL2A1 gene knock-in显示文摘Osteoarthritis(OA)is the most common chronic disease,characterized by progressive cartilage breakdown,subchondral bone sclerosis,and aberrant bone outgrowth(Yucesoy et al.,2015;Hussain et al.,2016).OA is one of the leading causes of cartilage damage.Patients with severe cartilage damage require transplantation of articular cartilage to improve their quality of life.Type Ⅱ collagen is a major component of articular cartilage and intervertebral discs and plays an important role in the structure and strength of connective tissues that support muscles and joints(Byers,1994). | Ting Lan Yuling Zheng Yangyang Suo Yuhui Wei Hui Shi Quanmei Yan Zhenpeng Zhuang Huangyao Chen Quanjun Zhang Nana Fan Yu Zhao Zhen Ouyang Chengdan Lai Zhaoming Liu Jizeng Zhou Chengcheng Tang Nam-Hyung Kim Qingjian Zou Xiaomin Wang | 2023 | Journal of Genetics and Genomics2023，50，3： | 0 |
| 4 | 敲入亨廷顿基因的猪模型再现了亨廷顿病的选择性神经退化症状显示文摘文章简介亨廷顿舞蹈病(Huntington’s disease, HD)是一种遗传性神经退行性疾病,是由一种编码导致脑细胞死亡的毒性蛋白的基因引起的。尽管转基因小鼠已被广泛用于构建神经退行性疾病模型,但是它们缺乏在人类大脑中观察到的典型神经变性或明显的神经元缺失。 | Sen Yan Zhuchi Tu Zhaoming Liu Nana Fan Huiming Yang Su Yang Weili Yang Yu Zhao Zhen Ouyang Chengdan Lai Huaqiang Yang Li Li Qishuai Liu Hui Shi Guangqing Xu Heng Zhao Hongjiang Wei Zhong Pei 李世华 赖良学 李晓江 | 2019 | 科学新闻2019，0，2： | 0 |
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