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| 1 | Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells显示文摘人的 pluripotent 干细胞代表功能的胰腺的内分泌的系房间的潜在地无限的来源。这里,我们报导一条高度有效的途径导致人的胚胎的茎(ES ) 细胞和导致的 pluripotent 茎(iPS ) 在一个定义化学药品的文化系统区分进成熟生产胰岛素的细胞的细胞。这条途径获得的区分的人的 ES 房间由流动 cytometry 分析作为 assayed 包括了将近 25% 胰岛素积极的房间,它以比得上成年人的小岛的一种方式响应葡萄糖刺激释放了 insulin/C-peptide。大多数这些生产胰岛素的房间共同表示成熟尾房间特定的标记象 NKX6-1 和 PDX1 那样,在 vivo 显示一个类似的基因表示模式到成年小岛尾房间。在这研究,我们也证明 EGF 便于 PDX1 积极的胰腺的祖先的扩大。而且,我们的协议也成功了高效地导致人的 iPS 房间区分进生产胰岛素的房间。因此,这个工作不仅提供一个新模型在 vitro 学习人的胰腺的专门化和成熟的机制,而且提高为糖尿病的处理利用病人特定的 iPS 房间的可能性。 | Donghui Zhang Wei Jiang Meng Liu Xin Sui Xiaolei Yin Song Chen Yan Shi Hongkui Deng | 2009 | Cell Research2009，19，4： | 90 |
| 2 | Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells显示文摘人的导致的 pluripotent 茎(iPS ) 房间类似于胚胎的茎(ES ) 房间,和罐头强烈地增殖并且区分进许多房间类型。然而,人的 iPS 房间的肝的区别还没被报导了。在这份报告,人的 iPS 房间被导致由一个逐步的协议区分进肝的房间。肝房间标记的表达式和人的 iPS 的肝相关的函数导出房间的房间被监视并且与区分的人的 ES 房间和主要人的 hepatocytes 的相比。在白天 7 点的约 60% 区分的人的 iPS 房间表示了肝的标记 alpha fetoprotein 和白长袍的。在白天 21 点的区分的房间包括白朊 Asecretion,肝糖合成,脲生产和可诱导的细胞色素 P450 活动展出了肝房间功能。肝的标记的表示和 iPS 的肝相关的功能导出房间的肝的房间比得上人的 ES 导出房间的肝的房间的。这些结果证明人的 iPS 房间,类似于人的 ES 房间,能高效地被导致区分房间进象 hepatocyte 一样。 | Zhihua Song Jun Cai Yanxia Liu Dongxin Zhao Jun Yong Shuguang Duo Xijun Song Yushan Guo Yang Zhao Han Qin Xiaolei Yin Chen Wu Jie Che Shichun Lu Mingxiao Ding Hongkui Deng | 2009 | Cell Research2009，19，11： | 63 |
| 3 | Generation of iPSCs from mouse fibroblasts with a single gene, Oct4, and small molecules显示文摘由病毒的 transduction 的四抄写因素 Oct4, Klf4, Sox2 和 c-Myc 的介绍能导致体的房间的 reprogramming 进导致的 pluripotent 干细胞(iPSCs ) ,但是 iPSCs 的使用被病毒的交货系统的使用妨碍。导致化学药品的 reprogramming 把一条新奇途径提供给没有任何病毒的基于向量的基因修正,产生 iPSCs。尽管,以前的报告证明几个小分子能代替一些 reprogramming 因素至少二个抄写因素, Oct4 和 Klf4,仍然被要求从老鼠产生 iPSCs 胚胎的成纤维细胞。这里,我们识别特定的化学联合,它是足够的面对一个单个抄写因素从胚胎的老鼠和成年成纤维细胞允许 reprogramming, Oct4 在 20 天以内,代替 Sox2, Klf4 和 c-Myc。用这个处理产生的 iPSCs 类似于胚胎的干细胞以全球基因表示介绍的老鼠,在 vitro 并且在 vivo 的 epigenetic 地位和 pluripotency。我们也发现那 8 天 Oct4 正式就职是足够的面对小分子启用导致 Oct4 的 reprogramming,它建议 reprogramming 在开始的 8 天以内被开始并且独立于连续外长的 Oct4 表示。没有基因修正,这些发现将帮助 iPSCs 的未来产生,以及阐明位于 reprogramming 过程下面的分子的机制。 | Yanqin Li Qiang Zhang Xiaolei Yin Weifeng Yang Yuanyuan Du Pingping Hou Jian Ge Chun Liu Weiqi Zhang Xu Zhang Yetao Wu Honggang Li Kang Liu Chen Wu Zhihua Song Yang Zhao Yan Shi Hongkui Deng | 2011 | Cell Research2011，21，1： | 51 |
| 4 | In vitro derivation of functional insulin-producing cells from human embryonic stem cells显示文摘为人的胚胎的茎(ES ) 的自强和区别的能力细胞为对待类型 Idiabetes mellitus 为胰腺的贝它细胞的产生使他们成为潜在的来源。这里,我们报导一最新发展了并且有效方法,在aserum免费的系统执行了,区分进生产胰岛素的 cells.Activin A 的导致的人的 ES 房间它在起始的阶段被使用从人的 EScells 导致权威的内胚叶区别,是由权威的内胚叶标记 Sox17 和 Brachyury.Further 的表示检测了, all-trans retinoic 酸( RA )被用来支持胰腺的区别,由早胰腺的抄写因素 pdx1 和 hlxb9 的表示显示了。在成熟 inDMEM/F12 以后有 bFGF 和菸碱的没有浆液的媒介,区分的房间表示了小岛特定的标记象 C 肽,胰岛素,胰高血糖素和 glut2 那样。百分比 ofC-peptide-positive 房间超过了 15% 。由这些房间的胰岛素和 C 肽的分泌物在葡萄糖层次对应于变化。当移植了进肾的囊时, ofStreptozotocin (STZ ) 对待裸体老鼠,这些区分的人的 ES 房间熬过并且维持贝它房间标记基因的表示包括 C 肽, pdx1, glucokinase, nkx6.1, IAPP, pax6and Tcf1。百分之三十只移植裸体老鼠展出了 stableeuglycemia 的明显的恢复;并且改正的显型被支撑超过六个星期。我们的新方法为学习人的胰开发的机制提供一个有希望的试管内区别模特儿并且说明为类型 Idiabetes mellitus 的处理使用人的 ES 房间的潜力。 | Wei Jiang Yan Shi Dongxin Zhao Song Chen Jun Yong Jing Zhang Tingting Qing Xiaoning Sun Peng Zhang Mingxiao Ding Dongsheng Li Hongkui Deng | 2007 | Cell Research2007，17，4： | 38 |
| 5 | Pluripotent stem cells induced from mouse neural stem cells and small intestinal epithelial cells by small molecule compounds显示文摘最近,我们报导了一条化学途径从老鼠成纤维细胞产生 pluripotent 干细胞。然而,是否化学上导致了 pluripotent 干细胞(CiPSCs ) ,能从要示威的另外的房间类型遗体被导出。用系跟踪,这里,我们首先从成纤维细胞验证 CiPSCs 的产生。下次,我们证明从外胚层的神经干细胞(NSC ) 和从内胚叶的小肠的上皮的房间(IEC ) 能是化学上 reprogrammed 进 pluripotent 干细胞。CiPSCs 源于 NSC 和 IEC 类似于老鼠处于增长率,全球基因表示侧面, epigenetic 地位,自强和区别能力的胚胎的干细胞,和 germline 传播才能。有趣地, pluripotency 基因 Sall4 从不同房间类型,和一样的核心在化学 reprogramming 过程在起始的阶段被表示小分子为 reprogramming 被要求,在从这些多样的房间类型位于化学 reprogramming 下面的分子的机制建议保存。我们的分析也证明这些小分子的使用应该被调整从不同房间类型满足 reprogramming 的要求。一起,这些调查结果证明那条完整的化学 reprogramming 途径能在不同织物起源的房间被使用并且建议化学 reprogramming 是有要延长到更起始的类型的潜力的有希望的策略。 | Junqing Ye Jian Ge Xu Zhang Lin Cheng Zhengyuan Zhang Shan He Yuping Wang Hua Lin Weifeng Yang Junfang Liu Yang Zhao Hongkui Deng | 2016 | Cell Research2016，26，1： | 19 |
| 6 | TGFβ inhibition enhances the generation of hematopoietic progenitors from human ES cell-derived hemogenic endothelial cells using a stepwise strategy显示文摘 | Chengyan Wang Xuming Tang Xiaomeng Sun Zhenchuan Miao Yaxin Lv Yanlei Yang Huidan Zhang Pengbo Zhang Yang Liu LiyingDu Yang Gao Ming Yin Mingxiao Ding Hongkui Deng | 2012 | Cell Research2012，22，1： | 17 |
| 7 | Piglets cloned from induced pluripotent stem cells显示文摘 | Nana Fan Jijun Chen Zhouchun Shang Hongwei Dou Guangzhen Ji Qingjian Zou Lu Wu Lixiazi He Fang Wang Kai Liu Na Liu Jianyong Han Qi Zhou Dengke Pan Dongshan Yang Bentian Zhao Zhen Ouyang Zhaoming Liu Yu Zhao Lin Lin Chongming Zhong Quanlei Wang Shouqi Wang Ying Xu Jing Luan Yu Liang Zhenzhen Yang Jing Li Chunxia Lu Gabor Vajta Ziyi Li Hongsheng Ouyang Huayan Wang Yong Wang Yang Yang Zhonghua Liu Hong Wei Zhidong Luan Miguel A Esteban Hongkui Deng Huanming Yang Duanqing Pei Ning Li Gang Pei Lin Liu Yutao Du Lei Xiao Liangxue Lai | 2013 | Cell Research2013，23，1： | 12 |
| 8 | Elimination of senescent cells byβ-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice显示文摘Cellular senescence,a persistent state of cell cycle arrest,accumulates in aged organisms,contributes to tissue dysfunction,and drives age-related phenotypes.The clearance of senescent cells is expected to decrease chronic,low-grade inflammation and improve tissue repair capacity,thus attenuating the decline of physical function in aged organisms.However,selective and effective clearance of senescent cells of different cell types has proven challenging.Herein,we developed a prodrug strategy to design a new compound based on the increased activity of lysosomalβ-galactosidase(β-gal),a primary characteristic of senescent cells.Our prodrug SSK1 is specifically activated byβ-gal and eliminates mouse and human senescent cells independently of senescence inducers and cell types.In aged mice,our compound effectively cleared senescent cells in different tissues,decreased the senescence-and age-associated gene signatures,attenuated low-grade local and systemic inflammation,and restored physical function.Our results demonstrate that lysosomalβ-gal can be effectively leveraged to selectively eliminate senescent cells,providing a novel strategy to develop anti-aging interventions. | Yusheng Cai Huanhuan Zhou Yinhua Zhu Qi Sun Yin Ji Anqi Xue Yuting Wang Wenhan Chen Xiaojie Yu Longteng Wang Han Chen Cheng Li Tuoping Luo Hongkui Deng | 2020 | Cell Research2020，30，7： | 12 |
| 9 | A two-step lineage reprogramming strategy to generate functionally competent human hepatocytes from fibroblasts显示文摘Terminally differentiated cells can be generated by lineage reprogramming,which is,however,hindered by incomplete conversion with residual initial cell identity and partial functionality. Here, we demonstrate a new reprogramming strategy by mimicking the natural regeneration route, which permits generating expandable hepatic progenitor cells and functionally competent human hepatocytes. Fibroblasts were first induced into human hepatic progenitor-like cells (hHPLCs), which could robustly expand in vitro and efficiently engraft in vivo. Moreover, hHPLCs could be efficiently induced into mature human hepatocytes (hiHeps) in vitro, whose molecular identity highly resembles primary human hepatocytes (PHHs). Most importantly, hiHeps could be generated in large quantity and were functionally competent to replace PHHs for drug-metabolism estimation, toxicity prediction and hepatitis B virus infection modeling. Our results highlight the advantages of the progenitor stage for successful lineage reprogramming. This strategy is promising for generating other mature human cell types by lineage reprogramming. | Bingqing Xie Da Sun Yuanyuan Du Jun Jia Shicheng Sun Jun Xu Yifang Liu Chengang Xiang Sitong Chen Huangfan Xie Qiming Wang Guangya Li Xuehui LYU Hui Shen Shiyu Li Min Wu Xiaonan Zhang Yue Pu Kuanhui Xiang Weifeng Lai Peng Du Zhenghong Yuan Cheng Li Yan Shi Shichun Lu Hongkui Deng | 2019 | Cell Research2019，29，9： | 9 |
| 10 | Establishment of intestinal organoid cultures modeling injury-associated epithelial regeneration显示文摘The capacity of 3D organoids to mimic physiological tissue organization and functionality has provided an invaluable tool to model development and disease in vitro.However,conventional organoid cultures primarily represent the homeostasis of self-organizing stem cells and their derivatives.Here,we established a novel intestinal organoid culture system composed of 8 components,mainly including VPA,EPZ6438,LDN193189,and R-Spondin 1 conditioned medium,which mimics the gut epithelium regeneration that produces hyperplastic crypts following injury;therefore,these organoids were designated hyperplastic intestinal organoids(Hyper-organoids).Single-cell RNA sequencing identified different regenerative stem cell populations in our Hyper-organoids that shared molecular features with in vivo injury-responsive Lgr5+stem cells or Clu+revival stem cells.Further analysis revealed that VPA and EPZ6438 were indispensable for epigenome reprogramming and regeneration in Hyper-organoids,which functioned through epigenetically regulating YAP signaling.Furthermore,VPA and EPZ6438 synergistically promoted regenerative response in gut upon damage in vivo.In summary,our results demonstrated a new in vitro organoid model to study epithelial regeneration,highlighting the importance of epigenetic reprogramming that pioneers tissue repair. | Molong Qu Liang Xiong Yulin Lyu Xiannian Zhang Jie Shen Jingyang Guan Peiyuan Chai Zhongqing Lin Boyao Nie Cheng Li Jun Xu Hongkui Deng | 2021 | Cell Research2021，31，3： | 9 |
| 11 | Hepatic spheroids derived from human induced pluripotent stem cells in bio-artificial liver rescue porcine acute liver failure显示文摘Dear Editor,Acute liver failure(ALF)is a complicated disorder showing a nearly 80%mortality rate,and there is currently no effective medical solutions for ALF except liver transplantation.1 Bio-artificial liver(BAL)system is a device that consists of a bioreactor filled with hepatocytes,which could potentially rescue ALF patients by providing partial liver function until a suitable donor liver can be found or the native liver has self-regenerated. | Sitong Chen Jinglin Wang Haozhen Ren Yinan Liu Chengang Xiang Cheng Li Shichun Lu Yan Shi Hongkui Deng Xiaolei Shi | 2020 | Cell Research2020，30，1： | 9 |
| 12 | GATA family members as inducers for cellular reprogramming to pluripotency显示文摘GATA 蛋白质家庭的成员在系说明和 transdifferentiation 起重要作用。以前的报告证明 GATA 蛋白质家庭罐头的一些成员也由代替 Oct4 在体的房间导致 pluripotency,一个关键联系 pluripotency 的因素。然而,连接指定系的暗示的机制和 pluripotency 的激活留下逃犯。这里,我们报导所有 GATA 家庭成员能代替让 Oct4 导致 pluripotency。我们发现 GATA 家庭的所有成员能禁止 overrepresented ectodermal 系基因,它与以前的报告显示不同指定系的力量的平衡为 pluripotency 的恢复是重要的一致。一根保存锌手指在 C 终点的 DNA 有约束力的领域是批评的让 GATA 家庭导致 pluripotency。用 RNA-seq 和 ChIP-seq,我们决定 pluripotency 相关的基因 Sall4 在 reprogramming 期间是 GATA 家庭成员的一个直接目标并且用作连接指定系的 GATA 家庭到 pluripotency 电路的一座桥。因此, GATA 家庭是所有成员能作为 reprogramming 进程的 inducers 工作并且能代替 Oct4 的第一个蛋白质家庭。我们的结果建议在 reprogramming 的 GATA 家庭的角色被低估了并且 GATA 家庭可以担任房间命运变换的一个重要调停人。 | Jian Shu Ke Zhang Minjie Zhang Yao Sida Shao Fengxia Du Caiyun Yang Wenhan Chen Chen Wu Weifeng Yang Yingli Sun Hongkui Deng | 2015 | Cell Research2015，25，2： | 5 |
| 13 | Pancreas-specific Pten deficiency causes partial resistance to diabetes and elevated hepatic AKT signaling显示文摘PTEN, phosphatidylinositol-3-kinase/AKT 小径的一个否定管理者,是胰岛素发信号的一个重要调节的人。决定胰腺的 Pten 的新陈代谢的函数,我们产生了胰特定的 Pten 大美人(PPKO ) 鼠标。PPKO 老鼠扩大了胰并且提高了 acinar 房间的增长。他们也展出了低血糖症, hypoinsulinemia,和改变的氨基的新陈代谢。尤其是, PPKO 老鼠证明 streptozotocin (STZ ) 的推迟的发作导致了糖尿病,到 high-fat-diet (HFD ) 的偏导性的抵抗导致了糖尿病。在 PPKO 老鼠为抵抗调查机制到导致 HFD 的多糖症,我们在主要胰岛素应答的纸巾评估了 AKT phosphorylation:肝,肌肉,和脂肪。我们发现在胰的 Pten 损失引起在肝发信号的 AKT 的举起。AKT 和它的下游的底层 GSK3 尾的 phosphorylation 在 PPKO 老鼠的肝被增加,当没有 Pten 等位基因的可检测的切除, PTEN 水平在 PPKO 老鼠的肝被减少时。戏剧性地揭示的 Proteomics 分析减少了在 PPKO 老鼠的肝 78-kDa 铺平调整葡萄糖的蛋白质(GRP78 ) ,它可以也贡献用 HFD 喂的 PPKO 老鼠的更低的血葡萄糖水平。一起,我们的调查结果在新陈代谢的规定在肝揭示新奇回答到胰腺的缺点,把一种新尺寸加到理解糖尿病抵抗。 | Zan Tong Yan Fan Weiqi Zhang Jun Xu Jing Cheng Mingxiao Ding Hongkui Deng | 2009 | Cell Research2009，19，6： | 5 |
| 14 | Pluripotent Stem Cells Induced from Mouse Somatic Cells by Small-Molecule Compounds显示文摘 | Pingping Hou Yanqin Li Xu Zhang Chun Liu Jingyang Guan Honggang Li Ting Zhao Junqing Ye Weifeng Yang Kang Liu Jian Ge Jun Xu Qiang Zhang Yang Zhao Hongkui Deng | 2013 | Science2013，，6146： | 4 |
| 15 | Systematically labeling developmental stage-specific genes for the study of pancreatic β-cell differentiation from human embryonic stem cells显示文摘 | Haisong Liu Huan Yang Dicong Zhu Xin Sui Juan Li Zhen Liang Lei Xu Zeyu Chen Anzhi Yao Long Zhang Xi Zhang Xing Yi Meng Liu Shiqing Xu Wenjian Zhang Hua Lin Lan Xie Jinning LOU Yong Zhang Jianzhong Xi Hongkui Deng | 2014 | Cell Research2014，24，10： | 3 |
| 16 | Isolation and characterization of liver epithelial progenitor cells from normal adult rhesus monkeys (Macaca mulatta)显示文摘 | Lifang Jin Shaohui Ji Xianghui Tang Xiangyu Guo Yongqing Lu Hongwei Chen Hongkui Deng Qi Zhou Weizhi Ji | 2009 | Cell Research2009，19，2： | 2 |
| 17 | Pluripotent Stem Cells Induced from Mouse Somatic Cells by Small-Molecule Compounds显示文摘 | Pingping Hou Yanqin Li Xu Zhang Chun Liu Jingyang Guan Honggang Li Ting Zhao Junqing Ye Weifeng Yang Kang Liu Jian Ge Jun Xu Qiang Zhang Yang Zhao Hongkui Deng | 2013 | Science . 2013 (6146)2013，，： | 2 |
| 18 | Pluripotent Stem Cells Induced from Mouse Somatic Cells by Small-Molecule Compounds显示文摘 | Pingping Hou Yanqin Li Xu Zhang Chun Liu Jingyang Guan Honggang Li Ting Zhao Junqing Ye Weifeng Yang Kang Liu Jian Ge Jun Xu Qiang Zhang Yang Zhao Hongkui Deng | 2013 | Science2013，，6146： | 2 |
| 19 | Promotion of the efficient metabolic maturation of human pluripotent stem cell-derived hepatocytes by correcting specification defects显示文摘 | Dongxin Zhao Song Chen Shuguang Duo Chengang Xiang Jun Jia Mina Guo Wei Lai Shichun LU Hongkui Deng | 2013 | Cell Research2013，23，1： | 2 |
| 20 | Generation of human hepatocytes from extended pluripotent stem cells显示文摘Dear Editor,Human pluripotent stem cells have great potential for application in regenerative medicine,as they permit the generation of different lineages of functional cell types via directed differentiation.1 However,application of conventional human pluripotent stem cells is limited due to several factors,including heterogeneity in pluripotency,differentiation bias,relatively slow proliferation,and poor single-cell survival.2 Toovercome these problems. | Qiming Wang Da Sun Zhen Liang Junyi Wang Xinxing Zhong Yulin Lyu Junning Cao Zhongqing Lin Yuanyuan Du Zhenchuan Miao Shichun Lu Cheng Li Jun Xu Yan Shi Hongkui Deng | 2020 | Cell Research2020，30，9： | 1 |
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