Human Pluripotent Stem Cell-Derived Intestinal Organoids Model SARS-CoV-2 Infection Revealing a Common Epithelial Inflammatory Response.
Human Pluripotent Stem Cell-Derived Intestinal Organoids Model SARS-CoV-2 Infection Revealing a Common Epithelial Inflammatory Response.
复制标题
DOI：
10.1016/j.stemcr.2021.02.019
复制
发表时间：
2021-04-13
影响因子：
5.9
通讯作者：
Mostoslavsky G
中科院分区：
文献类型：
--
作者：
Mithal A;Hume AJ;Lindstrom-Vautrin J;Villacorta-Martin C;Olejnik J;Bullitt E;Hinds A;Mühlberger E;Mostoslavsky G
严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）感染导致2019冠状病毒病（COVID-19）通常会导致呼吸道疾病，但肺外表现是主要的临床兴趣。COVID-19的肠道症状出现在相当多的患者中，包括恶心、腹泻和粪便中病毒RNA脱落。人类诱导多能干细胞衍生的肠道类器官（HIOs）是一种取之不尽的细胞资源，可以作为研究SARS-CoV-2以及其他感染肠上皮的肠道病毒的宝贵工具。在这里，我们报告了SARS-CoV-2有效感染近端和远端图案的HIOs，导致感染性病毒颗粒的释放，同时刺激强大的转录组反应，包括干扰素相关基因的显着上调，该基因似乎在多种上皮细胞类型中都是保守的。这些发现阐明了一种潜在的炎症上皮特异性特征，这可能有助于COVID-19的多系统性质及其高度可变的临床表现。人类ipsc衍生的肠道类器官易受SARS-CoV-2感染SARS-CoV-2感染伴随着HIO形态学的超微结构变化RNA-seq揭示了多种上皮细胞类型的共同炎症特征HIOs是模拟宿主对胃肠道感染性病原体反应的可行工具。及其同事利用ipsc衍生的区域模式肠道类器官模拟宿主对肠道SARS-CoV-2感染的反应。具体来说，他们强调了无间质肠道和结肠类器官的生产性感染，并证明它们概括了其他上皮细胞类型对感染的内在炎症转录组反应。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease 2019 (COVID-19) usually results in respiratory disease, but extrapulmonary manifestations are of major clinical interest. Intestinal symptoms of COVID-19 are present in a significant number of patients, and include nausea, diarrhea, and viral RNA shedding in feces. Human induced pluripotent stem cell-derived intestinal organoids (HIOs) represent an inexhaustible cellular resource that could serve as a valuable tool to study SARS-CoV-2 as well as other enteric viruses that infect the intestinal epithelium. Here, we report that SARS-CoV-2 productively infects both proximally and distally patterned HIOs, leading to the release of infectious viral particles while stimulating a robust transcriptomic response, including a significant upregulation of interferon-related genes that appeared to be conserved across multiple epithelial cell types. These findings illuminate a potential inflammatory epithelial-specific signature that may contribute to both the multisystemic nature of COVID-19 as well as its highly variable clinical presentation. Human iPSC-derived intestinal organoids are susceptible to productive SARS-CoV-2 infection SARS-CoV-2 infection is accompanied by ultrastructural changes in HIO morphology RNA-seq revealed a common inflammatory signature across multiple epithelial cell types HIOs are a viable tool to model host response to infectious pathogens in the GI tract In this article, Gustavo Mostoslavsky, Elke Mühlberger, and colleagues model the host response to intestinal SARS-CoV-2 infection using iPSC-derived regionally patterned intestinal organoids. Specifically, they highlight productive infection of mesenchyme-free intestinal and colonic organoids and demonstrate that they recapitulate intrinsic inflammatory transcriptomic responses to infection that have been shown in other epithelial cell types.
登录
查看更多内容
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
ACE2将氨基酸营养不良与微生物生态学和肠炎联系起来。
影响因子：
64.8
作者：
Hashimoto T;Perlot T;Rehman A;Trichereau J;Ishiguro H;Paolino M;Sigl V;Hanada T;Hanada R;Lipinski S;Wild B;Camargo SM;Singer D;Richter A;Kuba K;Fukamizu A;Schreiber S;Clevers H;Verrey F;Rosenstiel P;Penninger JM
通讯作者：
Penninger JM
危及生命的Covid-19患者中针对I型IFN的自身抗体。
DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bastard P;Rosen LB;Zhang Q;Michailidis E;Hoffmann HH;Zhang Y;Dorgham K;Philippot Q;Rosain J;Béziat V;Manry J;Shaw E;Haljasmägi L;Peterson P;Lorenzo L;Bizien L;Trouillet-Assant S;Dobbs K;de Jesus AA;Belot A;Kallaste A;Catherinot E;Tandjaoui-Lambiotte Y;Le Pen J;Kerner G;Bigio B;Seeleuthner Y;Yang R;Bolze A;Spaan AN;Delmonte OM;Abers MS;Aiuti A;Casari G;Lampasona V;Piemonti L;Ciceri F;Bilguvar K;Lifton RP;Vasse M;Smadja DM;Migaud M;Hadjadj J;Terrier B;Duffy D;Quintana-Murci L;van de Beek D;Roussel L;Vinh DC;Tangye SG;Haerynck F;Dalmau D;Martinez-Picado J;Brodin P;Nussenzweig MC;Boisson-Dupuis S;Rodríguez-Gallego C;Vogt G;Mogensen TH;Oler AJ;Gu J;Burbelo PD;Cohen JI;Biondi A;Bettini LR;D'Angio M;Bonfanti P;Rossignol P;Mayaux J;Rieux-Laucat F;Husebye ES;Fusco F;Ursini MV;Imberti L;Sottini A;Paghera S;Quiros-Roldan E;Rossi C;Castagnoli R;Montagna D;Licari A;Marseglia GL;Duval X;Ghosn J;HGID Lab;NIAID-USUHS Immune Response to COVID Group;COVID Clinicians;COVID-STORM Clinicians;Imagine COVID Group;French COVID Cohort Study Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19 Biobank;COVID Human Genetic Effort;Tsang JS;Goldbach-Mansky R;Kisand K;Lionakis MS;Puel A;Zhang SY;Holland SM;Gorochov G;Jouanguy E;Rice CM;Cobat A;Notarangelo LD;Abel L;Su HC;Casanova JL
通讯作者：
Casanova JL
影响因子：
23.9
作者：
Huang, Jessie;Hume, Adam J;Kotton, Darrell N
通讯作者：
Kotton, Darrell N
影响因子：
56.9
作者：
Lamers, Mart M.;Beumer, Joep;Clevers, Hans
通讯作者：
Clevers, Hans