Single-cell RNA sequencing analysis of SARS-CoV-2 entry receptors in human organoids.


Journal

Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222

Informations de publication

Date de publication:
04 2021
Historique:
received: 29 07 2020
revised: 01 09 2020
accepted: 07 09 2020
pubmed: 19 9 2020
medline: 20 2 2021
entrez: 18 9 2020
Statut: ppublish

Résumé

Coronavirus disease-2019 (COVID-19) is a global pandemic and caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has resulted in millions of deaths worldwide. Reports denote SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) as its primary entry point into the host cell. However, understanding the biology behind this viral replication, disease mechanism and drug discovery efforts are limited due to the lack of a suitable experimental model. Here, we used single-cell RNA sequencing data of human organoids to analyze expressions of ACE2 and TMPRSS2, in addition to an array of RNA receptors to examine their role in SARS-CoV-2 pathogenesis. ACE2 is abundant in all organoids, except the prostate and brain, and TMPRSS2 is omnipresent. Innate immune pathways are upregulated in ACE2(+) cells of all organoids, except the lungs. Besides this, the expression of low-density lipoprotein receptor is highly enriched in ACE2(+) cells in intestinal, lung, and retinal organoids, with the highest expression in lung organoids. Collectively, this study demonstrates that the organoids can be used as an experimental platform to explore this novel virus disease mechanism and for drug development.

Identifiants

pubmed: 32944935
doi: 10.1002/jcp.30054
pmc: PMC7537521
doi:

Substances chimiques

Receptors, Virus 0
ACE2 protein, human EC 3.4.17.23
Angiotensin-Converting Enzyme 2 EC 3.4.17.23
Serine Endopeptidases EC 3.4.21.-
TMPRSS2 protein, human EC 3.4.21.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2950-2958

Subventions

Organisme : American Heart Association
ID : 19TPA34880039 and 18IPA34170497

Informations de copyright

© 2020 Wiley Periodicals LLC.

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Auteurs

Rajasekaran Mahalingam (R)

Laboratory of Neuroimmunology, Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Prakash Dharmalingam (P)

Clonegene Biosystems, Chennai, Tamil Nadu, India.

Abirami Santhanam (A)

Ophthalmology and Visual Science, University of Texas Health Science center, Houston, Texas, USA.

Sivareddy Kotla (S)

Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Gangarao Davuluri (G)

Integrated Physiology and Molecular Metabolism, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.

Harry Karmouty-Quintana (H)

Department of Biochemistry and Molecular Biology & Divisions of Critical Care, Pulmonary and Sleep Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.

Guha Ashrith (G)

Department of Cardiology, Houston Methodist Hospital, Houston, Texas, USA.

Rajarajan A Thandavarayan (RA)

Department of Biochemistry and Molecular Biology & Divisions of Critical Care, Pulmonary and Sleep Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Department of Cardiology, Houston Methodist Hospital, Houston, Texas, USA.

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Classifications MeSH