翻譯 | 唐一塵

Science, 07 JUNE 2019, VOL 364, ISSUE 6444

《科學》2019年6月7日，第6444期364卷

類器官Organoids

Cancer modeling meets human organoid technology

癌症模型「遇見」人體器官技術

作者：David Tuveson、Hans Clevers

鏈接：

https://science.sciencemag.org/content/364/6444/952

摘要：

類器官是由幹細胞在體外培養而成的微觀自組織的三維結構。該技術推動產生了許多新的人類癌症模型。

本文綜述了快速發展的腫瘤類器官的研究現狀和前景。

研究人員表示，這讓他們第一次能從患者身上採集少量的腫瘤樣本，在實驗室中培養它們，將其構建成一個活生物資料庫，並可替代動物研究。

用這種方式研發的癌症類器官能對具體癌症患者進行個體藥物樣本測試，或在該類器官中製造癌性突變以理解其對疾病的具體促成作用。

Abstract

Organoids are microscopic self-organizing, three-dimensiona lstructures that are grown from stem cells in vitro. They recapitulate many structural and functional aspects of their in vivo counterpart organs. This versatile technology has led to the development of many novel human cancer models. It is now possible to create indefinitely expanding organoids starting from tumor tissue of individuals suffering from a range of carcinomas. Alternatively, CRISPR-based gene modification allows the engineering of organoid models of cancer through the introduction of any combination of cancer gene alterations to normal organoids. When combined with immune cells and fibroblasts, tumor organoids become models for the cancer microenvironment enabling immune-oncology applications. Emerging evidence indicates that organoids can be used to accurately predict drug responses in a personalized treatment setting. Here, we review the current state and future prospects of the rapidly evolving tumor organoid field.

Self-organization of stem cells into embryos: A window on early mammalian development

胚胎幹細胞的自組織：哺乳動物早期發育的窗口

作者：Marta N. Shahbazi、Eric D. Siggia、Magdalena Zernicka-Goetz

鏈接：

https://science.sciencemag.org/content/364/6444/948

摘要：

在不同規模的有機體中，健全而複雜的管理機制協調著胚胎髮育。由於胚胎體積小、不易獲得，植入後的活體研究尤其具有挑戰性。

本文對創建源於幹細胞的類器官樣胚胎構造如何能克服胚胎髮育研究中的困難進行了討論。

研究人員表示，胚胎幹細胞模型提供了一個強大的系統，用來分析這種複雜性。而對幾何形狀的控制、對物理環境的調節，以及對化學信號的啟動，揭示了胚胎幹細胞形成模式的內在能力。

研究人員還回顧了自組織的原理，以及它們是如何使細胞運動來產生胚胎的。

Abstract

Embryonic development is orchestrated by robust and complex regulatory mechanisms acting at different scales of organization. In vivo studies are particularly challenging for mammals after implantation, owing to the small size and inaccessibility of the embryo. The generation of stem cell models of the embryo represents a powerful system with which to dissect this complexity. Control of geometry, modulation of the physical environment, and priming with chemical signals reveal the intrinsic capacity of embryonic stem cells to make patterns. Adding the stem cells for the extra embryonic lineages generates three-dimensional models that are more autonomous from the environment and recapitulate many features of the pre- and postimplantation mouse embryo, including gastrulation. Here, we review the principles of self-organization and how they set cells in motion to create an embryo.

Organoids-on-a-chip

晶元上的類器官

作者：Sunghee Estelle Park、AndreiGeorgescu、Dongeun Huh

鏈接：

https://science.sciencemag.org/content/364/6444/960

摘要：

最近一系列研究闡釋了類器官技術在生物醫學研究中開闢新前沿的方式，隨著類器官技術開闢了生物醫學研究的新領域，對生產、控制和分析類器官及其微環境的創新工程方法的需求日益迫切。

在這篇綜述中，作者將探索晶元上的器官技術作為一個平台以滿足這一需求，並研究如何利用這項技術解決器官研究中的主要技術挑戰。

研究人員對將類器官與晶元上器官技術進行整合會如何令類器官更可能被應用於生物醫藥——包括對無法在人體中進行測試的場景，進行了分析。

儘管類器官能比晶元上器官技術更準確地建模人類機體，但類器官會以高度可變的方式發育，令其難以進行對照控制。

Abstract

Recent studies have demonstrated an array of stem cell–derived, self-organizing miniature organs, termed organoids, that replicate the key structural and functional characteristics of their in vivo counterparts. As organoid technology opens up new frontiers of research in biomedicine, there is an emerging need for innovative engineering approaches for the production, control, and analysis of organoids and their microenvironment. In this Review, we explore organ-on-a-chip technology as a platform to fulfill this need and examine how this technology may be leveraged to address major technical challenges in organoid research. We also discuss emerging opportunities and future obstacles for the development and application of organoid-on-a-chip technology.

生物學Biology

RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues

RNA序列分析揭示了正常組織的克隆擴增

作者：Keren Yizhak、Fran?oisAguet、Jaegil Kim、Gad Getz，et al

鏈接：

https://science.sciencemag.org/content/364/6444/eaaw0726

摘要：

隨著年齡增長，人體正常組織的健康細胞中會有突變累積。一般而言，被動累積的這些突變對細胞行為的影響可忽略不計。

然而，變異細胞會長成有害的變異克隆群，並被認為是數種疾病的源頭。

儘管有研究將正常組織內的克隆擴增與癌症掛鉤，但哪些特異性克隆最終會導致疾病的發生與發展仍不清楚。

本文提出了一種名為名為RNA-MuTect的新方法，它能用RNA測序數據檢測正常組織中的突變克隆並在正常組織中識別每個表達基因中的突變克隆，而非僅限於一小組表達基因。

將這種方法應用於來自癌症基因組圖譜和基因型—組織表達項目的RNA-seq數據，研究人員在37%的組織樣本中發現了克隆擴增，這些樣本代表了幾乎所有的（95%）捐贈個體。

有1/3的人在其基因組區域或基因中含有已知會有致癌作用的突變。這些結果顯示，某個組織的突變載荷與年齡、細胞增殖率及接觸外部致突變環境因子有關。

Abstract

How somatic mutations accumulate in normal cells is poorly understood. A comprehensive analysis of RNA sequencing data from ~6700 samples across 29 normal tissues revealed multiple somatic variants,demonstrating that macroscopic clones can be found in many normal tissues. We found that sun-exposed skin, esophagus, and lung have a higher mutation burden than other tested tissues, which suggests that environmental factors can promote somatic mosaicism. Mutation burden was associated with both age and tissue-specific cell proliferation rate, highlighting that mutations accumulate over both time and number of cell divisions. Finally, normal tissues were found to harbor mutations in known cancer genes and hot spots. This study provides abroad view of macroscopic clonal expansion in human tissues, thus serving as a foundation for associating clonal expansion with environmental factors, aging, and risk of disease.

Social transmission of food safety depends on synaptic plasticity in the prefrontal cortex

食物安全的社會傳播依賴於前額皮質突觸可塑性

作者：Micha?l Loureiro、Ridouane Achargui、ChristianLüscher，et al

鏈接：

https://science.sciencemag.org/content/364/6444/991

摘要：

當動物面對不熟悉的食物時，它的氣味，以及同種動物身上散發出的化學信息素，可以構成一種安全信息，並允許它們進食。

梨狀皮質負責嗅覺信息的編碼，而伏核（Nac）神經元的失活可以強烈地觸發消費行為。然而，嗅覺轉換為基於價值的行為的神經迴路和細胞底物仍然難以捉摸。

這裡，研究人員檢測到，在兩隻老鼠之間，針對NAc並接受梨狀皮質投射的內側前額葉皮層（mPFC）神經元在社交傳遞後活動增強。

研究人員發現，阻斷從梨狀皮質到mPFC的傳輸，也阻止了社交傳播。因此，mPFC中的突觸可塑性是食品安全社會傳播的細胞底物。

Abstract

When an animal is facing unfamiliar food, its odor, together with semio chemical semanating from a conspecific, can constitute a safety message and authorize intake. The piriform cortex (PiC) codes olfactory information, and the inactivation of neurons in the nucleus accumbens (NAc) can acutely trigger consumption. However, the neural circuit and cellular substrate of transition of olfactory perception into value-based actions remain elusive. We detected enhanced activity after social transmission between two mice in neurons of the medial prefrontal cortex (mPFC) that target the NAc and receive projections from the PiC. Exposure to a conspecific potentiated the excitatory post synaptic currents in NAc projectors, whereas blocking transmission from PiC to mPFC prevented social transmission. Thus, synaptic plasticity in the mPFC is acellular substrate of social transmission of food safety.

空間 /植物

Space/Plant Science

Aradio ridge connecting two galaxy clusters in a filament of the cosmic web

無線電波脊連接宇宙網路中的兩個星系團

作者：F. Govoni、E. Orrù、A. Bonafede，et al

鏈接：

https://science.sciencemag.org/content/364/6444/981

摘要：

星系團是宇宙中最巨大的組分，其包含的星系在數十至數百個之間，所涉質量巨大。跨越這些星系團間空間的是組成巨大宇宙網的暗條。

星系團形成於暗條連接處，並隨著它們的合併而通過集納宇宙物質成長，後者會產生可被觀測到的作為磁場和相對論粒子發射的能量。

研究人員用低頻陣列射電望遠鏡對ABELL 0399 和 ABELL 0401之間的區域進行了觀測。ABELL 0399 和 ABELL 0401是兩個合併中的巨型星系團。

儘管它們即將合併，但ABELL 0399 和 ABELL 0401仍然被近1000萬光年的星系間的遙遠距離隔開。

然而，在這一裂隙之間，研究人員檢測到一個連接這兩個星系團的低頻無線電發射脊。這些結果對目前的在這些廣袤星際空間中的粒子加速理論提出了挑戰。

Abstract

Galaxy clusters are the most massive gravitationally bound structures in the Universe. They grow by accreting smaller structures ina merging process that produces shocks and turbulence in the intracluster gas. We observed a ridge of radio emission connecting the merging galaxy clusters Abell 0399 and Abell 0401 with the Low-Frequency Array (LOFAR) telescope network at 140 megahertz. This emission requires a population of relativistic electrons and a magnetic field located in a filament between the two galaxy clusters. We performed simulations to show that a volume-filling distribution of weak shocks may reaccelerate a preexisting population of relativistic particles, producing emission at radio wave lengths that illuminates the magnetic ridge.

Eocene Fagaceae from Patagonia and Gondwanan legacy in Asian rainforests

亞洲熱帶雨林里的「遺產」

作者：Peter Wilf、Kevin C. Nixon、Maria A. Gandolfo、N. Rubén Cúneo

鏈接：

https://science.sciencemag.org/content/364/6444/eaaw5139

摘要：

從北溫帶到亞洲熱帶和馬來群島，山毛櫸—橡樹科的殼斗科植物佔據了叢林里的主導地位，它甚至達到了它的南部極限。

本論文報道了東南亞豐富多樣的殼斗科植物栲屬的始新世果序，以及阿根廷南部5200萬年前的Laguna del Hunco植物區系的同生葉。

值得注意的是，化石組合包括許多與栲屬有關的植物類群。這一發現揭示了殼斗科在岡瓦南的新歷史和東南亞低山地雨林特有的樹木群落。

研究人員表示，新生代的氣候變化和板塊運動持續了大量的散居生物群落，該研究也凸顯出相關植物目前易受快速氣候變化和棲息地喪失的影響。

Abstract

The beech-oak family Fagaceae dominates forests from the northern temperate zone to tropical Asia and Malesia, where it reaches its southern limit. We report early Eocene in fructescences of Castanopsis, a diverse and abundant fagaceous genus of Southeast Asia, and co-occurring leaves from the 52-million-year-old Laguna delHunco flora of southern Argentina. The fossil assemblage notably includes manyplant taxa that associate withCastanopsistoday. The discovery reveals novel Gondwanan history in Fagaceae and the characteristic tree communities of Southeast Asian lower-montane rainforests. The living diaspora associations persisted through Cenozoic climate change and plate movements as the constituent lineages tracked post-Gondwanan mesic biomesover thousands of kilometers, underscoring their current vulnerability to rapid climate change and habitat loss.

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