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nature论文导读 0914

时间: 2017年09月25日 | 作者: admin | 来源: 未知
1 【生物】 Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy 人类胶质细胞瘤 “命运图谱”揭示其恒有的干细胞层级结构 http://www.nature.com/nature/journal/v549/n7671/full/nature23666.html

1【生物】Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy

人类胶质细胞瘤“命运图谱”揭示其恒有的干细胞层级结构

http://www.nature.com/nature/journal/v549/n7671/full/nature23666.html 

Xiaoyang Lan et.al

 

(导读:阿金)人类胶质母细胞瘤中细胞异质性起源尚清楚。本研究使用异种移植方法发现,其细胞演化遵循着固有的层级分化历程:缓慢分裂的类干细胞分裂出快速分裂并可自我更新的癌祖细胞,祖细胞进一步产生不分裂的癌细胞。该研究还确认了化疗对于化疗抗性癌细胞的富集作用,提示使用不同表观遗传药物同时靶向多种癌细胞是胶质瘤治疗的新方法。

Human glioblastomas harbour a subpopulation of glioblastoma stem cells that drive tumorigenesis. However, the origin of intratumoural functional heterogeneity between glioblastoma cells remains poorly understood. Here we study the clonal evolution of barcoded glioblastoma cells in an unbiased way following serial xenotransplantation to define their individual fate behaviours. Independent of an evolving mutational signature, we show that the growth of glioblastoma clones in vivo is consistent with a remarkably neutral process involving a conserved proliferative hierarchy rooted in glioblastoma stem cells. In this model, slow-cycling stem-like cells give rise to a more rapidly cycling progenitor population with extensive self-maintenance capacity, which in turn generates non-proliferative cells. We also identify rare outlier clones that deviate from these dynamics, and further show that chemotherapy facilitates the expansion of pre-existing drug-resistant glioblastoma stem cells. Finally, we show that functionally distinct glioblastoma stem cells can be separately targeted using epigenetic compounds, suggesting new avenues for glioblastoma-targeted therapy.

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2【生物】Structural basis of MsbA-mediated lipopolysaccharide transport

MsbA介导脂多糖转运的结构基础 

http://www.nature.com/nature/journal/v549/n7671/full/nature23649.html 

Wei Mi et.al

图片1.png 

(导读:阿金)脂多糖是许多革兰氏阴性菌外膜上的一种分子,其合成位点在内膜的细胞质侧,MsbA蛋白可将其“翻面”至周质侧。本研究解析了MsbA蛋白在三个功能性状态下的单颗粒冷冻电镜结构,揭示了脂多糖如何结合MsbA以及MsbA如何反转脂多糖的过程,为了解其他类似蛋白质的架构特征开拓了新的道路。

Lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria is critical for the assembly of their cell envelopes. LPS synthesized in the cytoplasmic leaflet of the inner membrane is flipped to the periplasmic leaflet by MsbA, an ATP-binding cassette transporter. Despite substantial efforts, the structural mechanisms underlying MsbA-driven LPS flipping remain elusive. Here we use single-particle cryo-electron microscopy to elucidate the structures of lipid-nanodisc-embedded MsbA in three functional states. The 4.2Å-resolution structure of the transmembrane domains of nucleotide-free MsbA reveals that LPS binds deep inside MsbA at the height of the periplasmic leaflet, establishing extensive hydrophilic and hydrophobic interactions with MsbA. Two sub-nanometre-resolution structures of MsbA with ADP-vanadate and ADP reveal an unprecedented closed and an inward-facing conformation, respectively. Our study uncovers the structural basis for LPS recognition, delineates the conformational transitions of MsbA to flip LPS, and paves the way for structural characterization of other lipid flippases.

 

3【天文】Detection of titanium oxide in the atmosphere of a hot Jupiter

系外热木星大气中检测到氧化钛

http://www.nature.com/nature/journal/v549/n7671/full/nature23651.html

Elyar Sedaghati et.al

 (导读 阿金)研究人员通过测量透射光谱的微小变化、构建大气模型,能够推断系外行星大气的组成及属性。本研究报道了研究人员在一颗系外热木星行星WASP-19b大气中检测到了氧化钛(置信度7.7σ)、强散射雾霾(7.4σ)、钠(3.4σ)和水(7.9σ)。这一结果为进一步探索系外行星大气中的重元素开辟了道路,也为寻找第二地球提供新的可能性。

As an exoplanet transits its host star, some of the light from the star is absorbed by the atoms and molecules in the planets atmosphere, causing the planet to seem bigger; plotting the planets observed size as a function of the wavelength of the light produces a transmission spectrum. Measuring the tiny variations in the transmission spectrum, together with atmospheric modelling, then gives clues to the properties of the exoplanets atmosphere. Chemical species composed of light elementssuch as hydrogen, oxygen, carbon, sodium and potassiumhave in this way been detected in the atmospheres of several hot giant exoplanets, but molecules composed of heavier elements have thus far proved elusive. Nonetheless, it has been predicted that metal oxides such as titanium oxide (TiO) and vanadium oxide occur in the observable regions of the very hottest exoplanetary atmospheres, causing thermal inversions on the dayside. Here we report the detection of TiO in the atmosphere of the hot-Jupiter planet WASP-19b. Our combined spectrum, with its wide spectral coverage, reveals the presence of TiO (to a confidence level of 7.7σ), a strongly scattering haze (7.4σ) and sodium (3.4σ), and confirms the presence of water (7.9σ) in the atmosphere.

 

4【物理】Hardware-efficient variational quantum eigensolver for small molecules and quantum magnets

【封面故事】量子变分特征值解算器

http://www.nature.com/nature/journal/v549/n7671/full/nature23879.html

Abhinav Kandala et.al

(导读 阿金)由于传统的计算方法在处理电子结构问题时存在各种局限,研究人员将希望寄托于量子计算,但目前为止实验室环境下的量子模拟仅限于包含氢、氦的小分子系统。本研究利用量子变分特征值解算器将量子模拟的范围扩展至氢化铍(BeH2。另外,研究还证明了该方法可用于处理量子磁性问题。

Quantum computers can be used to address electronic-structure problems and problems in materials science and condensed matter physics that can be formulated as interacting fermionic problems, problems which stretch the limits of existing high-performance computers. Finding exact solutions to such problems numerically has a computational cost that scales  exponentially with the size of the system, and Monte Carlo methods are unsuitable owing to the fermionic sign problem. These limitations of classical computational methods have made solving even few-atom electronic-structure problems interesting for implementation  using medium-sized quantum computers. Yet experimental implementations  have so far been restricted to molecules involving only hydrogen and helium. Here we demonstrate the experimental optimization of Hamiltonian problems with up to six qubits and more than one hundred Pauli terms, determining the ground-state energy for molecules of increasing size, up to BeH2. We achieve this result by using a variational quantum eigenvalue solver (eigensolver) with efficiently prepared trial states that are tailored specifically to the interactions that are available in our quantum processor, combined with a compact encoding of fermionic Hamiltonians and a robust stochastic optimization routine. We demonstrate the flexibility of our approach by applying it to a problem of quantum magnetism, an antiferromagnetic Heisenberg model in an external magnetic field. In all cases, we find agreement between our experiments and numerical simulations using a model of the device with noise. Our results help to elucidate the requirements for scaling the method to larger systems and for bridging the gap between key problems in high-performance computing and their implementation on quantum hardware.

 

5【物理】Superparamagnetic enhancement of thermoelectric performance

超顺磁增强热电性能

http://www.nature.com/nature/journal/v549/n7671/full/nature23667.html

Qingjie Zhang(张清杰,武汉理工大学), Jihui Yang(杨继辉,华盛顿大学) et al.

(导读 阿金)在纳米尺度调控材料的化学和物理结构对于开发高性能热电材料十分重要。本论文通过将软磁材料的纳米颗粒嵌入热电材料基底,实现了对声子和电子传输性质的双重调控。纳米粒子的超顺磁性能够导致三种热电磁效应,从而有效地提高纳米复合材料的热电性能。

The ability to control chemical and physical structuring at the nanometre scale is important for developing high-performance thermoelectric materials. Progress in this area has been achieved mainly by enhancing phonon scattering and consequently decreasing the thermal conductivity of the lattice through the design of either interface structures at nanometre or mesoscopic length scales or multiscale hierarchical architectures. A nanostructuring approach that enables electron transport as well as phonon transport to be manipulated could potentially lead to further enhancements in thermoelectric performance. Here we show that by embedding nanoparticles of a soft magnetic material in a thermoelectric matrix we achieve dual control of phonon- and electron-transport properties. The properties of the nanoparticlesin particular, their superparamagnetic behaviour (in which the nanoparticles can be magnetized similarly to a paramagnet under an external magnetic field)lead to three kinds of thermoelectromagnetic effect: charge transfer from the magnetic inclusions to the matrix; multiple scattering of electrons by superparamagnetic fluctuations; and enhanced phonon scattering as a result of both the magnetic fluctuations and the nanostructures themselves. We show that together these effects can effectively manipulate electron and phonon transport at nanometre and mesoscopic length scales and thereby improve the thermoelectric performance of the resulting nanocomposites.

 

6【物理】Real-space imaging of non-collinear antiferromagnetic order with a single-spin magnetometer

通过单自旋磁力计实现非共线反铁磁序的实空间成像

http://www.nature.com/nature/journal/v549/n7671/full/nature23656.html

I. Gross, et.al

(导读 阿金)非共线反铁磁系统能够规避铁磁体的能耗等问题,并且更为易控、高效。本研究使用非侵入式单自旋磁力计,在室温下实现了铋铁氧体 (BiFeO3) 薄膜内非共线反铁磁序的实空间成像。这一成果对于研发下一代自旋电子器件具有重要意义。

Although ferromagnets have many applications, their large magnetization and the resulting energy cost for switching magnetic moments bring into question their suitability for reliable low-power spintronic devices. Non-collinear antiferromagnetic systems do not suffer from this problem, and often have extra functionalities: non-collinear spin order may break space-inversion symmetry and thus allow electric-field control of magnetism, or may produce emergent spinorbit effects6 that enable efficient spincharge interconversion. To harness these traits for next-generation spintronics, the nanoscale control and imaging capabilities that are now routine for ferromagnets must be developed for antiferromagnetic systems. Here, using a non-invasive, scanning single-spin magnetometer based on a nitrogenvacancy defect in diamond, we demonstrate real-space visualization of non-collinear antiferromagnetic order in a magnetic thin film at room temperature. We image the spin cycloid of a multiferroic bismuth ferrite thin film and extract a period of about 70 nanometres, consistent with values determined by macroscopic diffraction. In addition, we take advantage of the magnetoelectric coupling present in BiFeO3 to manipulate the cycloid propagation direction by an electric field. Besides highlighting the potential of nitrogenvacancy magnetometry for imaging complex antiferromagnetic orders at the nanoscale, these results demonstrate how BiFeO3 can be used in the design of reconfigurable nanoscale spin textures.

 

 

7【地球科学】Impact of a global temperature rise of 1.5 degrees Celsius on Asia’s glaciers

 

全球温度上升1.5摄氏度对亚洲冰川的影

 

http://www.nature.com/nature/journal/v549/n7671/full/nature23878.html

 

P. D. A. Kraaijenbrink et.al

图片2.png 

图片来源:nature

导读 郭思瑶)巴黎定希望将温度控制在高于前工业化水平1.5°C洲高山(HMA)冰川的影响未知。本研究发现该温度HMA意味着温度升高2.1±0.1°C64%±7%的冰川将会保留至本世末。四种气候模型预测都显示温度升高会给地区水资源管理造成严重的潜在危害。

 

Glaciers in the high mountains of Asia (HMA) make a substantial contribution to the water supply of millions of people and they are retreating and losing mass as a result of anthropogenic climate change at similar rates to those seen elsewhere. In the Paris Agreement of 2015, 195 nations agreed on the aspiration to limit the level of global temperature rise to 1.5 degrees Celsius (°C) above pre-industrial levels. However, it is not known what an increase of 1.5°C would mean for the glaciers in HMA. Here we show that a global temperature rise of 1.5°C will lead to a warming of 2.1±0.1°C in HMA, and that 64±7 per cent of the present-day ice mass stored in the HMA glaciers will remain by the end of the century. The 1.5°C goal is extremely ambitious and is projected by only a small number of climate models of the conservative IPCC’s Representative Concentration Pathway (RCP)2.6 ensemble. Projections for RCP4.5, RCP6.0 and RCP8.5 reveal that much of the glacier ice is likely to disappear, with projected mass losses of 49±7 per cent, 51±6 per cent and 64±5 per cent, respectively, by the end of the century; these projections have potentially serious consequences for regional water management and mountain communities.

 

8【生态】Biodiversity effects in the wild are common and as strong as key drivers of productivity

生物多样性在自然环境中作用广泛且生产力关键动力

http://www.nature.com/nature/journal/v549/n7671/full/nature23886.html

 

J. Emmett Duffy, et.al

 

More than 500 controlled experiments have collectively suggested that biodiversity loss reduces ecosystem productivity and stability. Yet the importance of biodiversity in sustaining the world’s ecosystems remains controversial, largely because of the lack of validation in nature, where strong abiotic forcing and complex interactions are assumed to swamp biodiversity effects. Here we test this assumption by analysing 133 estimates reported in 67 field studies that statistically separated the effects of biodiversity on biomass production from those of abiotic forcing. Contrary to the prevailing opinion of the previous two decades that biodiversity would have rare or weak effects in nature, we show that biomass production increases with species richness in a wide range of wild taxa and ecosystems. In fact, after controlling for environmental covariates, increases in biomass with biodiversity are stronger in nature than has previously been documented in experiments and comparable to or stronger than the effects of other well-known drivers of productivity, including climate and nutrient availability. These results are consistent with the collective experimental evidence that species richness increases community biomass production, and suggest that the role of biodiversity in maintaining productive ecosystems should figure prominently in global change science and policy.

 

(导读 郭怿暄)生物多样性维持生态系统生产力和稳定性的重要作用尚未在自然条件下证实。本研究在分离生物与非生物作用影响后对田野调查的估值进行分析,发现生物量生产力随生物多样性增加广泛存在,作用程度比实验室更强,指出生物多样性维持生态系统生产力的作用应在全球变化的科学和政策中占据突出地位。

 

9【生态】Early members of living fossil lineage imply later origin of modern ray-finned fishes

“活化石”谱系的早期成员暗示现代辐鳍鱼类的起源

http://www.nature.com/nature/journal/v549/n7671/full/nature23654.html

Sam Giles et.al

(导读:阿金)虽然一般认为白垩纪中期的多鳍鱼(Polypterid现代辐鳍鱼(Actinopterygii)起源于泥盆纪的最早分支,但古生代类群却与现代类群特征更相近。本研究发现三叠纪(约2.52-2.01亿年前)广泛分布的斯堪尼亚鱼类群(scanilepiforms)多鳍鱼干群,揭示现代辐鳍鱼许多原始特征实为返祖,并将辐鳍鱼冠群谱系起源年代后推约4千万年。  

 

Modern ray-finned fishes (Actinopterygii) comprise half of extant vertebrate species and are widely thought to have originated before or near the end of the Middle Devonian epoch (around 385million years ago). Polypterids (bichirs and ropefish) represent the earliest-diverging lineage of living actinopterygians , with almost all Palaeozoic taxa interpreted as more closely related to other extant actinopterygians than to polypterids. By contrast, the earliest material assigned to the polypterid lineage is mid-Cretaceous in age (around 100million years old)11, implying a quarter-of-a-billion-year palaeontological gap. Here we show that scanilepiforms, a widely distributed radiation from the Triassic period (around 252201million years ago), are stem polypterids. Importantly, these fossils break the long polypterid branch and expose many supposedly primitive features of extant polypterids as reversals. This shifts numerous Palaeozoic ray-fins to the actinopterygian stem, reducing the minimum age for the crown lineage by roughly 45million years. Recalibration of molecular clocks to exclude phylogenetically reassigned Palaeozoic taxa results in estimates that the actinopterygian crown lineage is about 2040million years younger than was indicated by previous molecular analyses. These new dates are broadly consistent with our revised palaeontological timescale and coincident with an interval of conspicuous morphological and taxonomic diversification among ray-fins centred on the DevonianCarboniferous boundary. A shifting timescale, combined with ambiguity in the relationships of late Palaeozoic actinopterygians, highlights this part of the fossil record as a major frontier in understanding the evolutionary assembly of modern vertebrate diversity.

 

 

10【生态】Kinetic analysis of a complete nitrifier reveals an oligotrophic lifestyle

硝化细菌动态分析揭示低营养的生活方式http://www.nature.com/nature/journal/v549/n7671/full/nature23679.html

K. Dimitri Kits, et.al

 (导读:阿金)本研究通过亚硝酸氧化细菌氧化菌(Nitrospira Inopinata)纯培养发现常规硝化细菌相比,其在低营养和动态环境中表现出高底物亲和力、低氨氧化率和产量缓慢生长,而古细菌(AOA并非贫瘠环境中竞争力最强的硝化。为了解贫瘠和动态环境中硝化作用提供新思路。

Nitrification, the oxidation of ammonia (NH3) via nitrite (NO2) to nitrate (NO3), is a key process of the biogeochemical nitrogen cycle. For decades, ammonia and nitrite oxidation were thought to be separately catalysed by ammonia-oxidizing bacteria  (AOB) and archaea (AOA), and by nitrite-oxidizing bacteria(NOB). The recent discovery of complete ammonia oxidizers (comammox) in the NOB genus Nitrospira, which alone convert ammonia to nitrate, raised questions about the ecological niches in which comammox Nitrospira successfully compete with canonical nitrifiers. Here we isolate a pure culture of a comammox bacterium, Nitrospira inopinata, and show that it is adapted to slow growth in oligotrophic and dynamic habitats on the basis of a high affinity for ammonia, low maximum rate of ammonia oxidation, high growth yield compared to canonical nitrifiers, and genomic potential for alternative metabolisms. The nitrification kinetics of four AOA from soil and hot springs were determined for comparison. Their surprisingly poor substrate affinities and lower growth yields reveal that, in contrast to earlier assumptions, AOA are not necessarily the most competitive ammonia oxidizers present in strongly oligotrophic environments and that N. inopinata has the highest substrate affinity of all analysed ammonia oxidizer isolates except the marine AOA Nitrosopumilus maritimus SCM1. These results suggest a role for comammox organisms in nitrification under oligotrophic and dynamic conditions.

 

11【生物】m6A modulates haematopoietic stem and progenitor cell specification

m6A调节造血干细胞和祖细胞的分化

http://www.nature.com/nature/journal/v549/n7671/full/nature23883.html

Chunxia Zhang, … Feng Liu(刘峰,动物所 & Yungui Yang(杨运桂,北京基因组研究所)

 

N6-methyladenosine (m6A) has been identified as the most abundant modification on eukaryote messenger RNA (mRNA). Although the rapid development of high-throughput sequencing technologies has enabled insight into the biological functions of m6A, the function of m6A during vertebrate embryogenesis remains poorly understood. Here we show that m6A determines cell fate during the endothelial-to-haematopoietic transition (EHT) to specify the earliest haematopoietic stem/progenitor cells (HSPCs) during zebrafish embryogenesis. m6A-specific methylated RNA immunoprecipitation combined with high-throughput sequencing (MeRIP–seq) and m6A individual-nucleotide-resolution cross-linking and immunoprecipitation with sequencing (miCLIP–seq) analyses reveal conserved features on zebrafish m6A methylome and preferential distribution of m6A peaks near the stop codon with a consensus RRACH motif. In mettl3-deficient embryos, levels of m6A are significantly decreased and emergence of HSPCs is blocked. Mechanistically, we identify that the delayed YTHDF2-mediated mRNA decay of the arterial endothelial genes notch1a and rhoca contributes to this deleterious effect. The continuous activation of Notch signalling in arterial endothelial cells of mettl3-deficient embryos blocks EHT, thereby repressing the generation of the earliest HSPCs. Furthermore, knockdown of Mettl3 in mice confers a similar phenotype. Collectively, our findings demonstrate the critical function of m6A modification in the fate determination of HSPCs during vertebrate embryogenesis.

 

(导读 郭怿暄)腺嘌呤N6甲基化修饰(m6A)是真核生物信使RNA最多的修饰。本研究揭示了斑马鱼中m6A的分布情况,并发现m6A可决定胚胎发育中内皮细胞向造血细胞转化的细胞命运,而这一作用是通过notch1arhocaNotch通路相关基因的mRNA调控而实现的。

 

 

12【生物】Neuronal regulation of type 2 innate lymphoid cells via neuromedin U

 

神经元通过神经介肽U调节2型天然淋巴细胞

 

 

http://www.nature.com/nature/journal/v549/n7671/full/nature23469.html

 

Vânia Cardoso, et.al

 

Group 2 innate lymphoid cells (ILC2s) regulate inflammation, tissue repair and metabolic homeostasis1, and are activated by host-derived cytokines and alarmins1. Discrete subsets of immune cells integrate nervous system cues2, 3, 4, but it remains unclear whether neuron-derived signals control ILC2s. Here we show that neuromedin U (NMU) in mice is a fast and potent regulator of type 2 innate immunity in the context of a functional neuron–ILC2 unit. We found that ILC2s selectively express neuromedin U receptor 1 (Nmur1), and mucosal neurons express NMU. Cell-autonomous activation of ILC2s with NMU resulted in immediate and strong NMUR1-dependent production of innate inflammatory and tissue repair cytokines. NMU controls ILC2s downstream of extracellular signal-regulated kinase and calcium-influx-dependent activation of both calcineurin and nuclear factor of activated T cells (NFAT). NMU treatment in vivo resulted in immediate protective type 2 responses. Accordingly, ILC2-autonomous ablation of Nmur1 led to impaired type 2 responses and poor control of worm infection. Notably, mucosal neurons were found adjacent to ILC2s, and these neurons directly sensed worm products and alarmins to induce NMU and to control innate type 2 cytokines. Our work reveals that neuron–ILC2 cell units confer immediate tissue protection through coordinated neuroimmune sensory responses.

 

(导读 逸轩)2型先天淋巴样细胞(ILC2s)是否神经来源信号调控尚不明确研究显示在小鼠黏膜神经元-ILC2细胞功能性单元中神经元释放的神经介肽U (NMU)ILC2s上的受体Nmur1结合,迅速激活炎症组织修复因子产生,快速有效调节2型先天免疫。结果揭示neuron–ILC2细胞单元通过协调神经免疫感知相应组织做出迅速保护。

 

13 【生物】The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation

 

神经介肽U刺激先天性淋巴细胞和2型炎症反应

 

http://www.nature.com/nature/journal/v549/n7671/full/nature23676.html

 

Christoph S. N. Klose, et.al

 

The type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 have important roles in stimulating innate and adaptive immune responses that are required for resistance to helminth infection, promotion of allergic inflammation, metabolic homeostasis and tissue repair1, 2, 3. Group 2 innate lymphoid cells (ILC2s) produce type 2 cytokines, and although advances have been made in understanding the cytokine milieu that promotes ILC2 responses4, 5, 6, 7, 8, 9, how ILC2 responses are regulated by other stimuli remains poorly understood. Here we demonstrate that ILC2s in the mouse gastrointestinal tract co-localize with cholinergic neurons that express the neuropeptide neuromedin U (NMU)10, 11. In contrast to other haematopoietic cells, ILC2s selectively express the NMU receptor 1 (NMUR1). In vitro stimulation of ILC2s with NMU induced rapid cell activation, proliferation, and secretion of the type 2 cytokines IL-5, IL-9 and IL-13 that was dependent on cell-intrinsic expression of NMUR1 and Gαq protein. In vivo administration of NMU triggered potent type 2 cytokine responses characterized by ILC2 activation, proliferation and eosinophil recruitment that was associated with accelerated expulsion of the gastrointestinal nematode Nippostrongylus brasiliensis or induction of lung inflammation. Conversely, worm burden was higher in Nmur1/ mice than in control mice. Furthermore, use of gene-deficient mice and adoptive cell transfer experiments revealed that ILC2s were necessary and sufficient to mount NMU-elicited type 2 cytokine responses. Together, these data indicate that the NMU–NMUR1 neuronal signalling circuit provides a selective mechanism through which the enteric nervous system and innate immune system integrate to promote rapid type 2 cytokine responses that can induce anti-microbial, inflammatory and tissue-protective type 2 responses at mucosal sites.

 

(导读 逸轩)2型先天淋巴样细胞(ILC2s)产生2型细胞因子白介素的刺激调控机制尚不清楚我们研究发现小鼠肠道内ILC2s与产生神经介肽 U (NMU)类胆碱神经元同区分布,ILC2s选择性表达NMU受体,二者形成神经环路共同实现2型细胞因子应答,在肠道产生迅速的免疫反应。

 

14【生物】Polycomb-like proteins link the PRC2 complex to CpG islands

多梳样蛋白将PRC2复合物与CpG岛连接

http://www.nature.com/nature/journal/v549/n7671/full/nature23881.html

Haojie Li,… Zhanxin Wang(王占新,北师大

 

The Polycomb repressive complex 2 (PRC2) mainly mediates transcriptional repression and has essential roles in various biological processes including the maintenance of cell identity and proper differentiation. Polycomb-like (PCL) proteins, such as PHF1, MTF2 and PHF19, are PRC2-associated factors that form sub-complexes with PRC2 core components, and have been proposed to modulate the enzymatic activity of PRC2 or the recruitment of PRC2 to specific genomic loci. Mammalian PRC2-binding sites are enriched in CG content, which correlates with CpG islands that display a low level of DNA methylation. However, the mechanism of PRC2 recruitment to CpG islands is not fully understood. Here we solve the crystal structures of the N-terminal domains of PHF1 and MTF2 with bound CpG-containing DNAs in the presence of H3K36me3-containing histone peptides. We show that the extended homologous regions of both proteins fold into a winged-helix structure, which specifically binds to the unmethylated CpG motif but in a completely different manner from the canonical winged-helix DNA recognition motif. We also show that the PCL extended homologous domains are required for efficient recruitment of PRC2 to CpG island-containing promoters in mouse embryonic stem cells. Our research provides the first, to our knowledge, direct evidence to demonstrate that PCL proteins are crucial for PRC2 recruitment to CpG islands, and further clarifies the roles of these proteins in transcriptional regulation in vivo.

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(导读 郭怿暄)多梳抑制复合体2(PRC2)在转录抑制中发挥重要作用。哺乳动物PRC2结合于基因组CpG岛,但其召集机制尚不清楚。本研究解析了多梳样蛋白(PCL)PHF1和MTF2的N端,与含有CpG及含H3K36me3组蛋白肽链的DNA相结合的的晶体结构,揭示了PCL结合DNA并召集PRC2的分子机制。