A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids

被引：502

作者：

Yang, Liuliu ^{[1
]}

Han, Yuling ^{[1
]}

Nilsson-Payant, Benjamin E. ^{[2
]}

Gupta, Vikas ^{[3
]}

Wang, Pengfei ^{[4
]}

Duan, Xiaohua ^{[1
,5
]}

Tang, Xuming ^{[1
]}

Zhu, Jiajun ^{[1
]}

Zhao, Zeping ^{[1
]}

Jaffre, Fabrice ^{[1
]}

Zhang, Tuo ^{[6
]}

Kim, Tae Wan ^{[7
,8
]}

Harschnitz, Oliver ^{[7
,8
]}

Redmond, David ^{[9
]}

Houghton, Sean ^{[9
]}

Liu, Chengyang ^{[10
]}

Naji, Ali ^{[10
]}

Ciceri, Gabriele ^{[7
,8
]}

Guttikonda, Sudha ^{[7
,8
,11
]}

Bram, Yaron ^{[3
]}

Nguyen, Duc-Huy T. ^{[3
]}

Cioffi, Michele ^{[12
,13
]}

Chandar, Vasuretha ^{[3
]}

Hoagland, Daisy A. ^{[2
]}

Huang, Yaoxing ^{[4
]}

Xiang, Jenny ^{[6
]}

Wang, Hui ^{[5
,14
]}

Lyden, David ^{[12
,13
]}

Borczuk, Alain ^{[15
]}

Chen, Huanhuan Joyce ^{[16
]}

Studer, Lorenz ^{[8
,9
]}

Pan, Fong Cheng ^{[1
]}

Ho, David D. ^{[4
]}

tenOever, Benjamin R. ^{[2
]}

Evans, Todd ^{[1
]}

Schwartz, Robert E. ^{[3
,17
]}

Chen, Shuibing ^{[1
]}

机构：

[1] Weill Cornell Med, Dept Surg, 1300 York Ave, New York, NY 10065 USA

[2] Icahn Sch Med Mt Sinai, Dept Microbiol, 1468 Madison Ave, New York, NY 10029 USA

[3] Weill Cornell Med, Dept Med, Div Gastroenterol & Hepatol, 1300 York Ave, New York, NY 10065 USA

[4] Columbia Univ, Vagelos Coll Phys & Surg, Aaron Diamond AIDS Res Ctr, New York, NY 10032 USA

[5] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China

[6] Weill Cornell Med, Genom Resource Core Facil, New York, NY 10065 USA

[7] Sloan Kettering Inst Canc Res, Ctr Stem Cell Biol, New York, NY 10065 USA

[8] Sloan Kettering Inst Canc Res, Dev Biol Program, New York, NY 10065 USA

[9] Weill Cornell Med, Ansary Stem Cell Inst, Div Regenerat Med, New York, NY 10065 USA

[10] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA

[11] Weill Cornell Rockefeller Sloan Kettering Triinst, New York, NY USA

[12] Weill Cornell Med, Meyer Canc Ctr, Childrens Canc & Blood Fdn Labs, Drukier Inst Childrens Hlth,Dept Pediat, New York, NY USA

[13] Weill Cornell Med, Meyer Canc Ctr, Dept Cell & Dev Biol, Drukier Inst Childrens Hlth, New York, NY USA

[14] Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes, Ctr Single Cell Omics, Sch Publ Hlth,Sch Med, Shanghai 200025, Peoples R China

[15] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA

[16] Univ Chicago, Ben May Dept Canc Res, Pritzker Sch Mol Engn, Chicago, IL 60637 USA

[17] Weill Cornell Med, Dept Physiol Biophys & Syst Biol, 1300 York Ave, New York, NY 10065 USA

来源：

CELL STEM CELL | 2020年 / 27卷 / 01期

基金：

美国国家卫生研究院;

关键词：

SARS CORONAVIRUS; GENE-EXPRESSION; COXSACKIE-B; ASSOCIATION; ISLETS; DIFFERENTIATION; NEUTRALIZATION; REPLICATION; LANGERHANS; CHILDREN;

D O I：

10.1016/j.stem.2020.06.015

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental platform comprised of cell and organoid derivatives from human pluripotent stem cells (hPSCs). A Spike-enabled pseudo-entry virus infects pancreatic endocrine cells, liver organoids, cardiomyocytes, and dopaminergic neurons. Recent clinical studies show a strong association with COVID-19 and diabetes. We find that human pancreatic beta cells and liver organoids are highly permissive to SARS-CoV-2 infection, further validated using adult primary human islets and adult hepatocyte and cholangiocyte organoids. SARS-CoV-2 infection caused striking expression of chemokines, as also seen in primary human COVID-19 pulmonary autopsy samples. hPSC-derived cells/organoids provide valuable models for understanding the cellular responses of human tissues to SARS-CoV-2 infection and for disease modeling of COVID-19.

引用

页码：125 / +

页数：19

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