Tongji University is a research-intensive university which takes a leading role in a large spectrum of researches from engineering to science, from medicine to arts in China, and even in the world. In recent years, more and more research results were published in reputed international journals while the majority of them in academic journals in China. We include publications inNature andSciencein the following, since it is impossible to provide an exhaustive list of publications in English, let alone those in Chinese.
1 Publications in Nature
(sources: https://www.nature.com/search?q=Tongji&order=date_desc&journal=nature&article_type=research)
1) Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1
November 28, 2018
2) Nuclear cGAS suppresses DNA repair and promotes tumorigenesis
October 24, 2018
3) Distinct features of H3K4me3 and H3K27me3 chromatin domains in pre-implantation embryos
September 14, 2016
4) Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing
July 28, 2013
5) Thin crust as evidence for depleted mantle supporting the Marion Rise
February 6, 2013
2 Publications in Science
1) Mineralogical control on the fate of continentally derived organic matter in the ocean
2) Cryo-EM structure of the mammalian ATP synthase tetramer bound with inhibitory protein IF1
3) The paraventricular thalamus is a critical thalamic area for wakefulness
4) Changes in the composition of brain interstitial ions control the sleep-wake cycle
1 Publications in Nature
1) Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1
Yingfeng Li,Zhuqiang Zhang,Jiayu Chen,Wenqiang Liu,Weiyi Lai,Baodong Liu,Xiang Li,Liping Liu,Shaohua Xu,Qiang Dong,Mingzhu Wang,Xiaoya Duan,Jiajun Tan,Yong Zheng,Pumin Zhang,Guoping Fan,Jiemin Wong,Guo-Liang Xu,Zhigao Wang,Hailin Wang,Shaorong Gao &Bing Zhu
Nature volume 564, pages136–140 (2018)
14k Accesses,14 Citations,67 Altmetric
Abstract
Postnatal growth of mammalian oocytes is accompanied by a progressive gain of DNA methylation, which is predominantly mediated by DNMT3A, a de novo DNA methyltransferase1,2. Unlike the genome of sperm and most somatic cells, the oocyte genome is hypomethylated in transcriptionally inert regions2,3,4. However, how such a unique feature of the oocyte methylome is determined and its contribution to the developmental competence of the early embryo remains largely unknown. Here we demonstrate the importance of Stella, a factor essential for female fertility5,6,7, in shaping the oocyte methylome in mice. Oocytes that lack Stella acquire excessive DNA methylation at the genome-wide level, including in the promoters of inactive genes. Such aberrant hypermethylation is partially inherited by two-cell-stage embryos and impairs zygotic genome activation. Mechanistically, the loss of Stella leads to ectopic nuclear accumulation of the DNA methylation regulator UHRF18,9, which results in the mislocalization of maintenance DNA methyltransferase DNMT1 in the nucleus. Genetic analysis confirmed the primary role of UHRF1 and DNMT1 in generating the aberrant DNA methylome in Stella-deficient oocytes. Stella therefore safeguards the unique oocyte epigenome by preventing aberrant de novo DNA methylation mediated by DNMT1 and UHRF1.
Access provided by Tongji University
https://www.nature.com/articles/s41586-018-0751-5.pdf
2) Nuclear cGAS suppresses DNA repair and promotes tumorigenesis
Haipeng Liu1,2 na1,Haiping Zhang3 na1,Xiangyang Wu1,2 na1,Dapeng Ma2,Juehui Wu1,2,Lin Wang1,2,Yan Jiang2,Yiyan Fei4,Chenggang Zhu4,Rong Tan5,Peter Jungblut6,GangPei7,Anca Dorhoi7,8,Qiaoling Yan2,Fan Zhang9,Ruijuan Zheng1,Siyu Liu2,Haijiao Liang1,2,Zhonghua Liu1,Hua Yang1,Jianxia Chen1,2,Peng Wang2,TianqiTang2,Wenxia Peng2,Zhangsen Hu3,Zhu Xu3,Xiaochen Huang1,Jie Wang1,Haohao Li1,Yilong Zhou1,2,Feng Liu1,Dapeng Yan10,Stefan H. E. Kaufmann7,Chang Chen9,Zhiyong Mao3 &Baoxue Ge1,2
Nature volume 563, pages131–136 (2018)
52k Accesses,35 Citations,54 Altmetric
Abstract
Accurate repair of DNA double-stranded breaks by homologous recombination preserves genome integrity and inhibits tumorigenesis. Cyclic GMP–AMP synthase (cGAS) is a cytosolic DNA sensor that activates innate immunity by initiating the STING–IRF3–type I IFN signalling cascade1,2. Recognition of ruptured micronuclei by cGAS links genome instability to the innate immune response3,4, but the potential involvement of cGAS in DNA repair remains unknown. Here we demonstrate that cGAS inhibits homologous recombination in mouse and human models. DNA damage induces nuclear translocation of cGAS in a manner that is dependent on importin-α, and the phosphorylation of cGAS at tyrosine 215—mediated by B-lymphoid tyrosine kinase—facilitates the cytosolic retention of cGAS. In the nucleus, cGAS is recruited to double-stranded breaks and interacts with PARP1 via poly(ADP-ribose). The cGAS–PARP1 interaction impedes the formation of the PARP1–Timeless complex, and thereby suppresses homologous recombination. We show that knockdown of cGAS suppresses DNA damage and inhibits tumour growth both in vitro and in vivo. We conclude that nuclear cGAS suppresses homologous-recombination-mediated repair and promotes tumour growth, and that cGAS therefore represents a potential target for cancer prevention and therapy.
Access provided by Tongji University
https://www.nature.com/articles/s41586-018-0629-6.pdf
3) Distinct features of H3K4me3 and H3K27me3 chromatin domains in pre-implantation embryos
Xiaoyu Liu,Chenfei Wang,Wenqiang Liu,Jingyi Li,Chong Li,Xiaochen Kou,Jiayu Chen,Yanhong Zhao,Haibo Gao,Hong Wang,Yong Zhang,Yawei Gao &Shaorong Gao
Nature volume 537, pages 558–562 (22 September 2016)
Abstract
Histone modifications have critical roles in regulating the expression of developmental genes during embryo development in mammals1,2. However, genome-wide analyses of histone modifications in pre-implantation embryos have been impeded by the scarcity of the required materials. Here, by using a small-scale chromatin immunoprecipitation followed by sequencing (ChIP–seq) method3, we map the genome-wide profiles of histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3), which are associated with gene activation and repression4,5, respectively, in mouse pre-implantation embryos. We find that the re-establishment of H3K4me3, especially on promoter regions, occurs much more rapidly than that of H3K27me3 following fertilization, which is consistent with the major wave of zygotic genome activation at the two-cell stage. Furthermore, H3K4me3 and H3K27me3 possess distinct features of sequence preference and dynamics in pre-implantation embryos. Although H3K4me3 modifications occur consistently at transcription start sites, the breadth of the H3K4me3 domain is a highly dynamic feature. Notably, the broad H3K4me3 domain (wider than 5 kb) is associated with higher transcription activity and cell identity not only in pre-implantation development but also in the process of deriving embryonic stem cells from the inner cell mass and trophoblast stem cells from the trophectoderm. Compared to embryonic stem cells, we found that the bivalency (that is, co-occurrence of H3K4me3 and H3K27me3) in early embryos is relatively infrequent and unstable. Taken together, our results provide a genome-wide map of H3K4me3 and H3K27me3 modifications in pre-implantation embryos, facilitating further exploration of the mechanism for epigenetic regulation in early embryos.
Access provided by Tongji University
https://www.nature.com/articles/nature19362.pdf
4) Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing
Zhigang Xue,Kevin Huang,Chaochao Cai,Lingbo Cai,Chun-yan Jiang,Yun Feng,Zhenshan Liu,Qiao Zeng,Liming Cheng,Yi E. Sun,Jia-yin Liu,Steve Horvath &Guoping Fan
Nature volume 500, pages 593–597 (29 August 2013)
Abstract
Mammalian pre-implantation development is a complex process involving dramatic changes in the transcriptional architecture1,2,3,4. We report here a comprehensive analysis of transcriptome dynamics from oocyte to morula in both human and mouse embryos, using single-cell RNA sequencing. Based on single-nucleotide variants in human blastomere messenger RNAs and paternal-specific single-nucleotide polymorphisms, we identify novel stage-specific monoallelic expression patterns for a significant portion of polymorphic gene transcripts (25 to 53%). By weighted gene co-expression network analysis5,6, we find that each developmental stage can be delineated concisely by a small number of functional modules of co-expressed genes. This result indicates a sequential order of transcriptional changes in pathways of cell cycle, gene regulation, translation and metabolism, acting in a step-wise fashion from cleavage to morula. Cross-species comparisons with mouse pre-implantation embryos reveal that the majority of human stage-specific modules (7 out of 9) are notably preserved, but developmental specificity and timing differ between human and mouse. Furthermore, we identify conserved key members (or hub genes) of the human and mouse networks. These genes represent novel candidates that are likely to be key in driving mammalian pre-implantation development. Together, the results provide a valuable resource to dissect gene regulatory mechanisms underlying progressive development of early mammalian embryos.
Access provided by Tongji University
https://www.nature.com/articles/nature12364.pdf
5) Thin crust as evidence for depleted mantle supporting the Marion Rise
Huaiyang Zhou &Henry J. B. Dick
Nature volume 494, pages 195–200 (14 February 2013)
Abstract
The global ridge system is dominated by oceanic rises reflecting large variations in axial depth associated with mantle hotspots. The little-studied Marion Rise is as large as the Icelandic Rise, considering both length and depth, but has an axial rift (rather than a high) nearly its entire length. Uniquely along the Southwest Indian Ridge systematic sampling allows direct examination of crustal architecture over its full length. Here we show that, unlike the Icelandic Rise, peridotites are extensively exposed high on the rise, revealing that the crust is generally thin, and often missing, over a rifted rise. Therefore the Marion Rise must be largely an isostatic response to ancient melting events that created low-density depleted mantle beneath the Southwest Indian Ridge rather than thickened crust or a large thermal anomaly. The origin of this depleted mantle is probably the mantle emplaced into the African asthenosphere during the Karoo and Madagascar flood basalt events.
Access provided by Tongji University
https://www.nature.com/articles/nature11842.pdf
2 Publications in Science
1) Mineralogical control on the fate of continentally derived organic matter in the ocean
T. M. Blattmann1,*,†, Z. Liu2,*, Y. Zhang2, Y. Zhao2, N. Haghipour1,3, D. B. Montluçon1, M. Plötze4, T. I. Eglinton1
1Geological Institute, ETH Zurich, Zurich, Switzerland.
2State Key Laboratory of Marine Geology, Tongji University, Shanghai, China.
3Laboratory of Ion Beam Physics, ETH Zurich, Zurich, Switzerland.
4Institute for Geotechnical Engineering, ETH Zurich, Zurich, Switzerland.
Science 03 Oct 2019:
eaax5345
DOI: 10.1126/science.aax5345
Abstract
First-order relationships between organic matter content and mineral surface area have been widely reported and are implicated in stabilization and long-term preservation of organic matter. However, the nature and stability of organo-mineral interactions and their connection with mineralogical composition, have remained uncertain. Here, we find that continentally derived organic matter of pedogenic origin is stripped from smectite mineral surfaces upon discharge, dispersal, and sedimentation in distal ocean settings. In contrast, organic matter sourced from ancient rocks that is tightly associated with mica and chlorite endures in the marine realm. These results imply that the persistence of continentally derived organic matter in ocean sediments is controlled to a first order by phyllosilicate mineralogy.
https://science.sciencemag.org/content/sci/early/2019/10/02/science.aax5345.full.pdf
2) Cryo-EM structure of the mammalian ATP synthase tetramer bound with inhibitory protein IF1
Jinke Gu1,*, Laixing Zhang1,*, Shuai Zong1,*, Runyu Guo1,*, Tianya Liu1, Jingbo Yi1, Peiyi Wang2, Wei Zhuo1, Maojun Yang1,3,†
1Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
2SUSTech Cryo-EM Facility Center, Southern University of Science and Technology, Shenzhen 518055, China.
3School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Science 14 Jun 2019:
Vol. 364, Issue 6445, pp. 1068-1075
DOI: 10.1126/science.aaw4852
ATP production under lockdown
Cellular processes must respond to change, often by speeding up, slowing down, or stopping altogether. Adenosine triphosphate (ATP) synthases use a transmembrane proton gradient to produce ATP, but this reaction can go in reverse and needs to be halted when conditions are unfavorable. Jinke Guet al. purified a tetrameric ATP synthase complex from pig hearts that contained the endogenous inhibitory protein IF1. Targeted refinement yielded high-resolution views of the mammalian ATP synthase trapped in two different rotation states by IF1. The findings suggest that ATP synthase tetramers can be inhibited by at least three different mechanisms.
Science, this issue p.1068
Abstract
The mitochondrial adenosine triphosphate (ATP) synthase produces most of the ATP required by mammalian cells. We isolated porcine tetrameric ATP synthase and solved its structure at 6.2-angstrom resolution using a single-particle cryo–electron microscopy method. Two classical V-shaped ATP synthase dimers lie antiparallel to each other to form an H-shaped ATP synthase tetramer, as viewed from the matrix. ATP synthase inhibitory factor subunit 1 (IF1) is a well-known in vivo inhibitor of mammalian ATP synthase at low pH. Two IF1 dimers link two ATP synthase dimers, which is consistent with the ATP synthase tetramer adopting an inhibited state. Within the tetramer, we refined structures of intact ATP synthase in two different rotational conformations at 3.34- and 3.45-Å resolution.
https://science.sciencemag.org/content/364/6445/1068.full.pdf
3) The paraventricular thalamus is a critical thalamic area for wakefulness
Shuancheng Ren1,*, Yaling Wang1,*, Faguo Yue1,2,*, Xiaofang Cheng1, Ruozhi Dang1, Qicheng Qiao1, Xueqi Sun1, Xin Li1, Qian Jiang2, Jiwei Yao3, Han Qin3, Guanzhong Wang1, Xiang Liao3, Dong Gao2, Jianxia Xia1, Jun Zhang1, Bo Hu1, Junan Yan3, Yanjiang Wang4, Min Xu5, Yunyun Han6, Xiangdong Tang7, Xiaowei Chen3,†, Chao He1,†, Zhian Hu1,†
1Department of Physiology, Collaborative Innovation Center for Brain Science, Third Military Medical University, Chongqing 400038, China.
2Department of Sleep and Psychology, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
3Brain Research Center, Third Military Medical University, Chongqing 400038, China.
4Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
5Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
6Department of Neurobiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
7Sleep Medicine Center, Laboratory of Anaesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, China.
Science 26 Oct 2018:
Vol. 362, Issue 6413, pp. 429-434
DOI: 10.1126/science.aat2512
A close view of the paraventricular thalamus
The paraventricular thalamus is a relay station connecting brainstem and hypothalamic signals that represent internal states with the limbic forebrain that performs associative functions in emotional contexts. Zhuet al. found that paraventricular thalamic neurons represent multiple salient features of sensory stimuli, including reward, aversiveness, novelty, and surprise. The nucleus thus provides context-dependent salience encoding. The thalamus gates sensory information and contributes to the sleep-wake cycle through its interactions with the cerebral cortex. Renet al. recorded from neurons in the paraventricular thalamus and observed that both population and single-neuron activity were tightly coupled with wakefulness.
Science, this issue p.423, p.429
Abstract
Clinical observations indicate that the paramedian region of the thalamus is a critical node for controlling wakefulness. However, the specific nucleus and neural circuitry for this function remain unknown. Using in vivo fiber photometry or multichannel electrophysiological recordings in mice, we found that glutamatergic neurons of the paraventricular thalamus (PVT) exhibited high activities during wakefulness. Suppression of PVT neuronal activity caused a reduction in wakefulness, whereas activation of PVT neurons induced a transition from sleep to wakefulness and an acceleration of emergence from general anesthesia. Moreover, our findings indicate that the PVT–nucleus accumbens projections and hypocretin neurons in the lateral hypothalamus to PVT glutamatergic neurons’ projections are the effector pathways for wakefulness control. These results demonstrate that the PVT is a key wakefulness-controlling nucleus in the thalamus.
https://science.sciencemag.org/content/sci/362/6413/429.full.pdf
4) Changes in the composition of brain interstitial ions control the sleep-wake cycle
Fengfei Ding1,2,*, John O’Donnell1,*, Qiwu Xu1, Ning Kang1, Nanna Goldman1, Maiken Nedergaard1,3,†
1Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
2Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
3Center for Basic and Translational Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
Science 29 Apr 2016:
Vol. 352, Issue 6285, pp. 550-555
DOI: 10.1126/science.aad4821
Sleep induction through ion changes
How do we switch from sleep to arousal and back? Dinget al. found that a combination of modulatory neurotransmitters influenced the levels of extracellular ions in the brain (see the Perspective by Landolt and Holst). This influence was not driven by changes in local neuronal firing, suggesting direct effects of the neuromodulators on extracellular ion composition. However, these changes in interstitial ion levels could switch a brain from wakefulness to sleep. Changes in extracellular ions may thus be a cause, rather than a consequence, of sleep/wake-dependent changes in neuronal activity.
Science, this issue p.550; see also p.517
Abstract
Wakefulness is driven by the widespread release of neuromodulators by the ascending arousal system. Yet, it is unclear how these substances orchestrate state-dependent, global changes in neuronal activity. Here, we show that neuromodulators induce increases in the extracellular K+ concentration ([K+]e) in cortical slices electrically silenced by tetrodotoxin. In vivo, arousal was linked to AMPA receptor–independent elevations of [K+]e concomitant with decreases in [Ca2+]e, [Mg2+]e, [H+]e, and the extracellular volume. Opposite, natural sleep and anesthesia reduced [K+]e while increasing [Ca2+]e, [Mg2+]e, and [H+]e as well as the extracellular volume. Local cortical activity of sleeping mice could be readily converted to the stereotypical electroencephalography pattern of wakefulness by simply imposing a change in the extracellular ion composition. Thus, extracellular ions control the state-dependent patterns of neural activity.
https://science.sciencemag.org/content/352/6285/550.full.pdf
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