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| 1 | Direct conversion of human fibroblasts into retinal pigment epithelium-like cells by defined factors显示文摘功能的网膜的颜料上皮(RPE ) 的产生具有到再生药的地的大治疗学的兴趣并且可以为网膜的退化疾病提供可能的痊愈,包括年龄相关的有斑点的退化(AMD ) 。尽管 RPE 房间能从胚胎的干细胞被生产或导致了 pluripotent 干细胞,决定系的抄写因素驾驶的直接房间 reprogramming 提供一条立即的线路给他们的产生。由监视人的 RPE 特定的 Best1::GFP 记者,我们报导进 RPE 系使用的人的成纤维细胞的变换定义抄写因素的集合。我们发现 Best1::GFP 积极房间形成了殖民地并且展出了早阶段 RPE 房间的词法、分子的特征。而且,他们能在 Retinoic 酸(RA ) 和表明小径的声音的刺猬(嘘) 的激活之上获得色素沉着。我们的学习不仅建立了一个理想的平台调查调整 RPE 房间命运决心的 transcriptional 网络,而且提供了其他的策略产生为疾病建模,屏蔽的药,和网膜的退化的房间治疗补充 pluripotent 干细胞的使用的功能的 RPE 房间。 | Kejing Zhang Guang-Hui Liu Fei Yi Nuria Montserrat Tomoaki Hishida Concepcion Rodriguez Esteban Juan Carlos Izpisua Belmonte] | 2014 | Protein & Cell2014,5,1: | 6 |
| 2 | A widely adaptable approach to generate integration-free iPSCs from non-invasively acquired human somatic cells显示文摘 | Zhichao Ding Lina Sui Ruotong Ren Yanjun Liu Xiuling Xu Lina Fu Ruijun Bai Tingting Yuan Ying Hao Weiqi Zhang Huize Pan Wensu Liu Han Yu Concepcion Rodriguez Esteban Xiaobing Yu Ze Yang Jian Li Xiaomin Wang Juan Carlos Izpisua Belmonte Guang-Hui Liu Fei Yi Jing Qu | 2015 | Protein & Cell2015,6,5: | 5 |
| 3 | Precise in vivo genome editing via single homology arm donor mediated intron-targeting gene integration for genetic disease correction显示文摘In vivo genome editing represents a powerful strategy for both understanding basic biology and treating inherited diseases.However,it remains a challenge to develop universal and efficient in vivo genome-editing tools for tissues that comprise diverse cell types in either a dividing or non-dividing state.Here,we describe a versatile in vivo gene knock-in methodology that enables the targeting of a broad range of mutations and cell types through the insertion of a minigene at an intron of the target gene locus using an intracellularly linearized single homology arm donor.As a proof-of-concept,we focused on a mouse model of prematureaging caused by a dominant point mutation,which is difficult to repair using existing in vivo genome-editing tools.Systemic treatment using our new method ameliorated aging-associated phenotypes and extended animal lifespan,thus highlighting the potential of this methodology for a broad range of in vivo genome-editing applications. | Keiichiro Suzuki Mako Yamamoto Reyna Hernandez-Benitez Zhe Li Christopher Wei Rupa Devi Soligalla Emi Aizawa Fumiyuki Hatanaka Masakazu Kurita Pradeep Reddy Alejandro Ocampo Tomoaki Hishida Masahiro Sakurai Amy NNemeth Estrella Nunez Delicado Josep MCampistol Pierre Magistretti Pedro Guillen Concepcion Rodriguez Esteban Jianhui Gong Yilin Yuan Ying Gu Guang-Hui Liu Carlos Lopez-Otin Jun Wu Kun Zhang Juan Carlos Izpisua Belmonte | 2019 | Cell Research2019,29,10: | 2 |
| 4 | αKLOTHO and sTGFβR2 treatment counteract the osteoarthritic phenotype developed in a rat model显示文摘Dear Editor,Homeostasis and repair are critical biological processes that allow for tissue and organ preservation and function in multicellular organisms.Their regulation and extension vary drastically across the animal kingdom,and mammals show limited tissue-specific regenerative capacity that declines with age.During aging,articular cartilage is one of the tissues that undergo substantial changes in the matrix structure,molecular composition,metabolic activity,and mechanical properties(Loeser et al.2016). | Paloma Martinez-Redondo Isabel Guillen-Guillen Noah Davidsohn Chao Wang Javier Prieto Masakazu Kurita Fumiyuki Hatanaka Cuiqing Zhong Reyna Hernandez-Benitez Tomoaki Hishida Takashi Lezaki Akihisa Sakamoto Amy NNemeth Yuriko Hishida Concepcion Rodriguez Esteban Kensaku Shojima Ling Huang Maxim Shokhirev Estrella Nunez-Delicado Josep MCampistol Isabel Guillen-Vicente Elena Rodriguez-Inigo Juan Manuel Lopez-Alcorocho Marta Guillen-Vicente George Church Pradeep Reddy Pedro Guillen-Garcia Guang-Hui Liu Juan Carlos Izpisua Belmonte | 2020 | Protein & Cell2020,11,3: | 2 |
| 5 | FOXO3-engineered human mesenchymal progenitor cells efficiently promote cardiac repair after myocardial infarction显示文摘Dear Editor,Myocardial infarction(MI)is the irreversible cardiomyocyte death resulting from prolonged oxygen deprivation due to obstructed blood supply(ischemia),leading to contractile dysfunction and cardiac remodeling.In recent decades,stem cell transplantation has been extensively investigated for the repair of injured heart in animal studies and clinical trials(Kanelidis et al.,2017;Gyongyosi et al.,2018). | Jinghui Lei Si Wang Wang Kang Qun Chu Zunpeng Liu Liang Sun Yun Ji Concepcion Rodriguez Esteban Yan Yao Juan Carlos Izpisua Belmonte Piu Chan Guang-Hui Liu Weiqi Zhang Moshi Song Jing Qu | 2021 | Protein & Cell2021,12,2: | 1 |
| 6 | Mutations in foregut SOX2^+ cells induce efficient proliferation via CXCR2 pathway显示文摘Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2^+ foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras^G12D and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2^+ cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras^G12D expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics. | Tomoaki Hishida Eric Vazquez-Ferrer Yuriko Hishida-Nozaki Ignacio Sancho-Martinez Yuta Takahashi Fumiyuki Hatanaka Jun Wu Alejandro Ocampo Pradeep Reddy Min-Zu Wu Laurie Gerken Reuben J. Shaw Concepcion Rodriguez Esteban Christopher Benner Hiroshi Nakagawa Pedro Guillen Garcia Estrella Nunez Delicado Antoni Castells Josep M. Campistol Guang-Hui Liu Juan Carlos Izpisua Belmonte | 2019 | Protein & Cell2019,10,7: | 1 |
| 7 | Global DNA methylation and transcriptional analyses of human ESC-derived cardiomyocytes显示文摘与定义文化协议,人的胚胎的干细胞(hESCs ) 能在 vitro 产生 cardiomyocytes,因此为人的心开发提供一个伟大的模型,并且保持为心脏病治疗的大潜力。在这研究,我们成功地产生了人的 cardiomyocytes (hCMs ) 的一张高度纯的人口(>95%cTnT+) 从 hESC,在基因表示和 DNA methylation 的线,使我们能识别并且描绘 hCM 特定的签名,铺平。这些充实 hCM 的基因的基因功能的协会网络和基因疾病网络分析提供新卓见进 hCM transcriptional 规定的机制,并且为调查心脏的基因函数和疾病机制作为一个增进知识、富有的资源站。而且,我们证明心脏结构的基因和心脏抄写的因素有不同 epigenetic 机制调整他们的基因表示,提供 epigenetic 机械怎么协调在不同房间调整基因表示的更好的理解打字。 | Ying Gut Guang-Hui Liu Nongluk Plongthongkum' Christopher Benner Fei Yi Jing Qu Keiichiro Suzuki Jiping Yang Weiqi Zhang Mo Li Nuria Montserrat Isaac Crespo Antonio del Sol Concepcion Rodriguez Esteban Kun Zhang Juan Carlos Izpisua Belmonte | 2014 | Protein & Cell2014,5,1: | 0 |