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| 1 | Correction of a genetic disease by CRISPR-Cas9-mediated gene editing in mouse spermatogonial stem cells显示文摘Spermatogonial 干细胞(SSC ) 能在移植以后生产众多的男配偶子进接受者睾丸,介绍为基因治疗和修改基因的动物的连续生产的一条珍贵途径。然而, SSC 的成功的基因操作被限制了,部分由于复杂性和当前可得到的基因编辑技术的低效率。这里,我们证明有效基因修正能用 CRISPR-Cas9 系统被介绍进 SSC。我们使用了 CRISPR-Cas9 系统变异在 SCC 的 EGFP transgene 或内长的 Crygc 基因。变异的 SSC 在移植以后经历了精子发生进不肥沃的老鼠睾丸的生精的小管。圆 spermatids 被产生并且在进成熟卵母细胞的注射以后,支持了显示相应变异的显型的异质接合的后代的生产。而且,在 Crygc 的一个引起疾病的变化(在 SSC 先存在的 Crygc −/−) 能乐意地到加入的 CRISPR-Cas9-induced nonhomologous 结束(NHEJ ) 或指导相同的修理(HDR ) 被修理,导致没有是的离开目标修正的证据带改正的基因的 SSC 线由整个染色体的定序出现。用从这些线产生的圆 spermatids 的授精在 100% 的效率与改正的显型产生了后代。我们的结果表明有效基因由 CRISPR-Cas9 系统在老鼠 SSC 编辑,并且提供在 SSC 经由基因修正治好基因疾病的原则的证明。 | Yuxuan Wu Hai Zhou Xiaoying Fan Ying Zhang Man Zhang Yinghua Wang Zhenfei Xie Meizhu Bai Qi Yin Dan Liang Wei Tang Jiaoyang Liao Chikai Zhou Wujuan Liu Ping Zhu Hongshan Guo Hong Pan Chunlian Wu Huijuan Shi Ligang Wu Fuchou Tang Jinsong Li | 2015 | Cell Research2015，25，1： | 37 |
| 2 | Single-cell multi-omics sequencing of mouse early embryos and embryonic stem cells显示文摘定序技术的单个房间的 epigenome 最近被开发了。然而,在一个单个房间定序的 epigenome 的不同的层的联合还没被完成了。这里,我们开发了定序能分析染色质的技术(单个房间的 COOL-seq ) 的单个房间的 multi-omics 放的 state/nucleosome, DNA methylation,拷贝数字变化和 ploidy 同时从一样的单个哺乳动物的房间。我们使用了这个方法在老鼠 preimplantation 胚胎分析染色质状态和 DNA methylation 的 reprogramming。我们发现了那在以内 < 授精的 12 h,每个单个房间和母亲、父亲的染色体的快速、全球的 reprogramming 经历全球染色体 demethylation 到一个高度打开的染色质状态。这被减少的坦诚在迟了的接合子阶段以后跟随。而且,从迟了的接合子上演到 4 房间,剩余 DNA methylation 优先地在各单个的分裂球在父亲的等位基因的 intergenic 区域和母亲的等位基因的 intragenic 区域上被保存。然而,染色质可接近性在在从迟了的接合子的每个单个房间的父亲、母亲的等位基因之间是类似的到胚囊阶段。几个 pluripotency 管理者的有约束力的主题在远侧的 nucleosome 被充实弄空的区域从象 2 房间阶段一样早。这显示如此的目标基因的 cis 规章的元素从 2 房间阶段被告知到一个开的状态向前,在 pluripotency 最后在胚囊的 ICM 被建立以前,渴望。基因可以被分类进同类地开,同类地关门了并且分叉的状态基于他们在单个房间之中的倡导者区域的染色质可接近性。这能在 preimplantation 开发期间被跟踪到逐步的转变。我们的学习在早老鼠胚胎在单个底的分辨率提供染色体规模染色质状态和 DNA methylation 动力学的第一单个房间、父母的等位基因特定的分析并且提供新卓见进异构还高度在这个过程期间订了 epigenomic reprogramming 的特征。 | Fan Guo Lin Li Jingyun Li Xinglong Wu Boqiang Hu Ping Zhu Lu Wen Fuchou Tang | 2017 | Cell Research2017，27，8： | 34 |
| 3 | Single-cell RNA-seq uncovers dynamic processes and critical regulators in mouse spermatogenesis显示文摘 | Yao Chen Yuxuan Zheng Yun Gao Zhen Lin Suming Yang Tongtong Wang Qiu Wang Nannan Xie Rong Hua Mingxi Liu Jiahao Sha Michael D. Griswold Jinsong Li Fuchou Tang Ming-Han Tong | 2018 | Cell Research2018，28，9： | 26 |
| 4 | Genome-scale detection of hypermethylated CpG islands in circulating cell-free DNA of hepatocellular carcinoma patients显示文摘 | Lu Wen Jingyi Li Huahu Guo Xiaomeng Liu Shengmin Zheng Dafang Zhang Weihua Zhu Jianhui Qu Limin Guo Dexiao Du Xiao Jin Yuhao Zhang Yun Gao Jie Shen Hao Ge Fuchou Tang Yanyi Huang Jirun Peng | 2015 | Cell Research2015，25，11： | 19 |
| 5 | Genetic enhancement in cultured human adult stem cells conferred by a single nucleotide recoding显示文摘 | Jiping Yang Jingyi Li Keiichiro Suzuki Xiaomeng Liu Jun Wu Weiqi Zhang Ruotong Ren Weizhou Zhang Piu Chan Juan Carlos Izpisua Belmonte Jing Qu Fuchou Tang Guang-Hui Liu | 2017 | Cell Research2017，27，9： | 12 |
| 6 | Spatial transcriptomic survey of human embryonic cerebral cortex by single-cell RNA-seq analysis显示文摘人的大脑开发的细胞的复杂性强烈地被调查了,尽管全部人的服的外皮的地区性的描述没基于单个房间的 transcriptome 分析被报导。这里,我们从人的中间怀孕期的胚胎的 22 个大脑区域在超过 4,000 个单个房间上执行了 RNA-seq。我们识别了 29 房间亚簇,它证明在每个区域和脑桥的不同比例显示出星形细胞的特别高的百分比。胚胎的神经原不象成年神经原一样多样,尽管他们在成年人拥有了他们的命运的重要特征。神经原开发是在服的外皮的 unsynchronized,当背面的区域看起来比在这个阶段的腹的区域更成熟。区域特定的基因包括地在每 neuronal 亚簇被识别,并且这些基因的一个大比例是联系的神经疾病。我们的结果介绍区域化的基因表示的一处系统的风景和人的服的外皮的神经原成熟。 | Xiaoying Fan Ji Dong Suijuan Zhong Yuan Wei Qian Wu Liying Yan Jun Yong Le Sun Xiaoye Wang Yangyu Zhao Wei Wang Jie Yan Xiaoqun Wang Jie Qiao Fuchou Tang | 2018 | Cell Research2018，28，7： | 11 |
| 7 | Meningeal lymphatic vessels regulate brain tumor drainage and immunity显示文摘Recent studies have shown that meningeal lymphatic vessels(MLVs),which are located both dorsally and basally beneath the skull,provide a route for draining macromolecules and trafficking immune cells from the central nervous system(CNS)into cervical lymph nodes(CLNs),and thus represent a potential therapeutic target for treating neurodegenerative and neuroinflammatory diseases.However,the roles of MLVs in brain tumor drainage and immunity remain unexplored.Here we show that dorsal MLVs undergo extensive remodeling in mice with intracranial gliomas or metastatic melanomas.RNA-seq analysis of MLV endothelial cells revealed changes in the gene sets involved in lymphatic remodeling,fluid drainage,as well as inflammatory and immunological responses.Disruption of dorsal MLVs alone impaired intratumor fluid drainage and the dissemination of brain tumor cells to deep CLNs(dCLNs).Notably,the dendritic cell(DC)trafficking from intracranial tumor tissues to dCLNs decreased in mice with defective dorsal MLVs,and increased in mice with enhanced dorsal meningeal lymphangiogenesis.Strikingly,disruption of dorsal MLVs alone,without affecting basal MLVs or nasal LVs,significantly reduced the efficacy of combined anti-PD-1/CTLA-4 checkpoint therapy in striatal tumor models.Furthermore,mice bearing tumors overexpressing VEGF-C displayed a better response to anti-PD-1/CTLA-4 combination therapy,and this was abolished by CCL21/CCR7 blockade,suggesting that VEGF-C potentiates checkpoint therapy via the CCL21/CCR7 pathway.Together,the results of our study not only demonstrate the functional aspects of MLVs as classic lymphatic vasculature,but also highlight that they are essential in generating an efficient immune response against brain tumors. | Xueting Hu Qiuping Deng Lu Ma Qingqing Li Yidong Chen Yuhan Liao Fan Zhou Chen Zhang Linlin Shao Jun Feng Tubao He Weihai Ning Yan Kong Yingqing Huo Aibin He Bing Liu Jingjing Zhang Ralf Adams Yulong He Fuchou Tang Xiuwu Bian Jincai Luo | 2020 | Cell Research2020，30，3： | 11 |
| 8 | Oocyte-expressed yes-associated protein is a key activator of the early zygotic genome in mouse显示文摘 | Chao Yu Shu-Yan Ji Yu-Jiao Dang Qian-Qian Sha Yi-FengYuan Jian-Jie Zhou Li-Ying Yan Jie Qiao Fuchou Tang Heng-Yu Fan | 2016 | Cell Research2016，26，3： | 9 |
| 9 | Embryonic endothelial evolution towards first hematopoietic stem cells revealed by single-cell transcriptomic and functional analyses显示文摘Hematopoietic stem cells(HSCs)in adults are believed to be born from hemogenic endothelial cells(HECs)in mid-gestational embryos.Due to the rare and transient nature,the HSC-competent HECs have never been stringently identified and accurately captured,let alone their genuine vascular precursors.Here,we first used high-precision single-cell transcriptomics to unbiasedly examine the relevant EC populations at continuous developmental stages with intervals of 0.5 days from embryonic day(E)9.5 to E11.0.As a consequence,we transcriptomically identified two molecularly different arterial EC populations and putative HSCprimed HECs,whose number peaked at El 0.0 and sharply decreased thereafter,in the dorsal aorta of the aorta-gonadmesonephros(AGM)region.Combining computational prediction and in vivo functional validation,we precisely captured HSCcompetent HECs by the newly constructed Neurl3-EGFP reporter mouse model,and realized the enrichment further by a combination of surface markers(Procr+Kit+CD44+,PK44).Surprisingly,the endothelial-hematopoietic dual potential was rarely but reliably witnessed in the cultures of single HECs.Noteworthy,primitive vascular ECs from E8.0 experienced two-step fate choices to become HSC-primed HECs,namely an Initial arterial fate choice followed by a hemogenic fate conversion.This finding resolves several previously observed contradictions.Taken together,comprehensive understanding of endothelial evolutions and molecular programs underlying HSC-primed HEC specification in vivo will facilitate future investigations directing HSC production in vitro. | Siyuan Hou Zongcheng Li Xiaona Zheng Yun Gao Ji Dong Yanli Ni Xiaobo Wang Yunqiao Li Xiaochen Ding Zhilin Chang Shuaili Li Yuqiong Hu Xiaoying Fan Yu Hou Lu Wen Bing Liu Fuchou Tang Yu Lan | 2020 | Cell Research2020，30，5： | 8 |
| 10 | Recent advances in mammalian reproductive biology显示文摘Reproductive biology is a uniquely important topic since it is about germ cells, which are central for transmitting genetic information from generation to generation. In this review, we discuss recent advances in mammalian germ cell development,including preimplantation development, fetal germ cell development and postnatal development of oocytes and sperm. We also discuss the etiologies of female and male infertility and describe the emerging technologies for studying reproductive biology such as gene editing and single-cell technologies. | Lu Wen Qiang Liu Jingjing Xu Xixi Liu Chaoyi Shi Zuwei Yang Yili Zhang Hong Xu Jiang Liu Hui Yang Hefeng Huang Jie Qiao Fuchou Tang Zi-Jiang Chen | 2020 | Science China(Life Sciences)2020，63，1： | 6 |
| 11 | Silencing of developmental genes by H3K27me3 and DNA methylation reflects the discrepant plasticity of embryonic and extraembryonic lineages显示文摘 | Xianfa Yang Boqiang Hu Yu Hou Yunbo Qiao Ran Wang Yingying Chen Yun Qian Su Feng Jun Chen Chang Liu Guangdun Peng Fuchou Tang Naihe Jing | 2018 | Cell Research2018，28，5： | 5 |
| 12 | Derivation of hypermethylated pluripotent embryonic stem cells with high potency显示文摘天真的 hypomethylated 胚胎的 pluripotent 干细胞(转换字符) 离胚囊的 preimplantation epiblast 发展地最靠近,与潜力到贡献所有胚胎的纸巾和 germline,除了在妄想的胚胎的胚胎外的纸巾。由对比,类似于 postimplantation epiblast 的 epiblast 干细胞(EpiSCs ) 是相对更多的 methylated 和表演为 chimerism 的一个有限潜力。第一次,这里,我们在 pluripotent 房间以外发展地揭示先进 pluripotent 干细胞(ASC ) ,它是在内部房间团中,但是与更高的力量比 EpiSCs。因此,单个 ASC 在怪物很高效地作出贡献到胎儿, germline,蛋黄囊和胎盘的迷宫。因为他们是,发展地,更多进展了, ASC 不贡献 trophoblast。ASC 在与 Activin A 和基本成纤维细胞生长因素补充的化学上定义的媒介在二个步骤从胚囊被导出,在包含 ActA, BMP4, CHIR99021 和白血病的 ABCL 媒介由 culturing 列在后面禁止的因素。尤其是, ASC 与天真的 pluripotency 基因,以及 mesodermal 的表示展出不同 transcriptome 体的基因;Eomes,时代, Tdgf1, Evx1, hand1, Wnt5a 和不同重复元素。到 ASC 的确定的转换字符的变换也是可完成的。重要地, ASC 作为与 hypomethylated 相比展出稳定的 hypermethylated epigenome 和主要未经触动的印记胚囊和天真的转换字符的内部房间质量。ASC 的性质建议他们以在 pluripotency 的天真、告知的状态之间的一个中间的细胞的状态代表房间。 | Siqin Bao Walfred WC Tang Baojiang Wu Shinseog Kim Jingyun Li Lin Li Toshihiro Kobayashi Caroline Lee Yanglin Chen Mengyi Wei Shudong Li Sabine Dietmann Fuchou Tang Xihe Li | 2018 | Cell Research2018，28，1： | 4 |
| 13 | Surveying brain tumor heterogeneity by single-cell RNA-sequencing of multi-sector biopsies显示文摘Brain tumors are among the most challenging human tumors for which the mechanisms driving progression and heterogeneity remain poorly understood.We combined single-cell RNA-seq with multi-sector biopsies to sample and analyze single-cell expression profiles of gliomas from 13 Chinese patients.After classifying individual cells;we generated a spatial and temporal landscape of glioma that revealed the patterns of invasion between the different sub-regions of gliomas.We also used single-cell inferred copy number variations and pseudotime trajectories to inform on the crucial branches that dominate tumor progression.The dynamic cell components of the multi-region biopsy analysis allowed us to spatially deconvolute with unprecedented accuracy the transcriptomic features of the core and those of the periphery of glioma at single-cell level.Through this rich and geographically detailed dataset,we were also able to characterize and construct the chemokine and chemokine receptor interactions that exist among different tumor and non-tumor cells.This study provides the first spatial-level analysis of the cellular states that characterize human gliomas.It also presents an initial molecular map of the cross-talks between glioma cells and the surrounding microenvironment with single-cell resolution. | Kai Yu Yuqiong Hu Fan Wu Qiufang Guo Zenghui Qian Waner Hu Jing Chen Kuanyu Wang Xiaoying Fan Xinglong Wu John EJ Rasko Xiaolong Fan Antonio lavarone Tao Jiang Fuchou Tang Xiao-Dong Su | 2020 | National Science Review2020，7，8： | 4 |
| 14 | Deciphering primate retinal aging at single-cell resolution显示文摘Dear Editor, The retina is a light-sensitive highly-organized tissue,which is vulnerable to aging and age-related retinal diseases.Specifically,progressive retinal degeneration leads to visual function deterioration and vision impairment in the elderly(Lin et al.,2016).In diseases such as age-related macular degeneration(AMD),retinitis pigmentosa(RP)and diabetic retinopathy(DR),pathological process lacking effective treatments profoundly and negatively impact on the quality of life in the elderly(Lin et al.,2016;Chen et al.,2019).Thus,an in-depth molecular assessment of the mechanisms driv-ing retinal aging is of urgent scientific and medical importance. | Si Wang Yuxuan Zheng Qingqing Li Xiaojuan He Ruotong Ren Weiqi Zhang Moshi Song Huifang Hu Feifei Liu Guoqiang Sun Shuhui Sun Zunpeng Liu Yang Yu Piu Chan Guo-Guang Zhao Qi Zhou Guang-Hui Liu Fuchou Tang Jing Qu | 2021 | Protein & Cell2021，12，11： | 4 |
| 15 | Clonal analysis reveals remarkable functional heterogeneity during hematopoietic stem cell emergence显示文摘 | Hui Ye Xiaobo Wang Zongcheng Li Fan Zhou Xianlong Li Yanli Ni Weijing Zhang Fuchou Tang Bing Liu Yu Lan | 2017 | Cell Research2017，27，8： | 4 |
| 16 | H3K4me3 epigenomic landscape derived from ChIP-Seq of 1000 mouse early embryonic cells显示文摘 | Jie Shen Dongqing Jiang Yusi Fu Xinglong Wu Hongshan Guo Binxiao Feng Yuhong Pang Aaron M Streets Fuchou Tang Yanyi Huang | 2015 | Cell Research2015，25，1： | 4 |
| 17 | A single-cell transcriptomic atlas of primate pancreatic islet aging显示文摘Aging-related degeneration of pancreatic islet cells contributes to impaired glucose tolerance and diabetes.Endocrine cells age heterogeneously,complicating the efforts to unravel the molecular drivers underlying endocrine aging.To overcome these obstacles,we undertook single-cell RNA sequencing of pancreatic islet cells obtained from young and aged non-diabetic cynomolgus monkeys.Despite sex differences and increased transcriptional variations,agedβ-cells showed increased unfolded protein response(UPR)along with the accumulation of protein aggregates.We observed transcriptomic dysregulation of UPR components linked to canonical ATF6 and IRE1 signaling pathways,comprising adaptive UPR during pancreatic aging.Notably,we found aging-relatedβ-cell-specific upregulation of HSP90 B1,an endoplasmic reticulum-located chaperone,impeded high glucose-induced insulin secretion.Our work decodes aging-associated transcriptomic changes that underlie pancreatic islet functional decay at single-cell resolution and indicates that targeting UPR components may prevent loss of proteostasis,suggesting an avenue to delayingβ-cell aging and preventing aging-related diabetes. | Jingyi Li Yuxuan Zheng Pengze Yan Moshi Song Si Wang Liang Sun Zunpeng Liu Shuai Ma Juan Carlos Izpisua Belmonte Piu Chan Qi Zhou Weiqi Zhang Guang-Hui Liu Fuchou Tang Jing Qu | 2021 | National Science Review2021，8，2： | 3 |
| 18 | In vitro expansion of human sperm through nuclear transfer显示文摘Dear Editor,Mammalian haploid embryonic stem cells(haESCs)represent an ideal tool for genetic analysis due to the presence of only one set of genetic materials.HaESCs fall into two readily distinguishable groups based on their genome origins:parthenogenetic haESCs(PG-haESCs)that are derived from oocyte-originated parthenogenetic embryos and androgenetic haESCs(AG-haESCs)that are produced through sperm nuclear transfer.Both PG-and AGhaESCs are feasible for delineating genome function at cellular level in vitro.Importantly,AG-haESCs can be used as a sperm replacement and applied to deciphering gene function at organismal level when combined with CRISPR-Cas9 technology.1 However,while PG-haESCs have been generated from both rodent and primates,2-5 AG-haESCs can only be obtained in rodent to date. | Xiaoyu Merlin Zhang Keliang Wu Yuxuan Zheng Han Zhao Junpeng Gao Zhenzhen Hou Meiling Zhang Jiaoyang Liao Jingye Zhang Yuan Gao Yuanyuan Li Lin Li Fuchou Tang Zi-Jiang Chen Jinsong Li | 2020 | Cell Research2020，30，4： | 3 |
| 19 | Refined spatial temporal epigenomic profiling reveals intrinsic connection between PRDM9-mediated H3K4me3 and the fate of double-stranded breaks显示文摘Meiotic recombination is initiated by the formation of double-strand breaks(DSBs),which are repaired as either crossovers(COs)or noncrossovers(NCOs).In most mammals,PRDM9-mediated H3K4me3 controls the nonrandom distribution of DSBs;however,both the timing and mechanism of DSB fate control remain largely undetermined.Here,we generated comprehensive epigenomic profiles of synchronized mouse spermatogenic cells during meiotic prophase I,revealing spatiotemporal and functional relationships between epigenetic factors and meiotic recombination.We find that PRDM9-mediated H3K4me3 at DSB hotspots,coinciding with H3K27ac and H3K36me3,is intimately connected with the fate of the DSB.Our data suggest that the fate decision is likely made at the time of DSB formation:earlier formed DSBs occupy more open chromatins and are much more competent to proceed to a CO fate.Our work highlights an intrinsic connection between PRDM9-mediated H3K4me3 and the fate decision of DSBs,and provides new insight into the control of CO homeostasis. | Yao Chen Ruitu Lyu Bowen Rong Yuxuan Zheng Zhen Lin Ruofei Dai Xi Zhang Nannan Xie Siqing Wang Fuchou Tang Fei Lan Ming-Han Tong | 2020 | Cell Research2020，30，3： | 3 |
| 20 | Heterogeneity in endothelial cells and widespread venous arterialization during early vascular development in mammals显示文摘Arteriogenesis rather than unspecialized capillary expansion is critical for restoring effective circulation to compromised tissues in patients.Deciphering the origin and specification of arterial endothelial cells during embryonic development will shed light on the understanding of adult arteriogenesis.However,during early embryonic angiogenesis,the process of endothelial diversification and molecular events underlying arteriovenous fate settling remain largely unresolved in mammals.Here,we constructed the single-cell transcriptomic Iandscape of vascular endothelial cells(VECs)during the time window for the occurrenee of key vasculogenic and angiogenic events in both mouse and human embryos.We uncovered two distinct arterial VEC types,the major artery VECs and arterial plexus VECs,and un expectedly diverge nt arteriove nous characteristics among VECs that are located in morphologically undistinguishable vascular plexus intra-embryonically.Using computational prediction and further lineage tracing of venous-featured VECs with a newly developed Nr2f2^(CrexER) | Siyuan Hou Zongcheng Li Ji Dong Yun Gao Zhilin Chang Xiaochen Ding Shuaili Li Yunqiao Li Yang Zeng Qian Xin Baihan Wang Yanli Ni Xiaowei Ning Yuqiong Hu Xiaoying Fan Yu Hou Xianlong Li Lu Wen Bin Zhou Bing Liu Fuchou Tang Yu Lan | 2022 | Cell Research2022，32，4： | 2 |
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