Journal article
Parallel use of human stem cell lung and heart models provide insights for SARS-CoV-2 treatment
R Rudraraju, MJ Gartner, JA Neil, ES Stout, J Chen, EJ Needham, M See, C Mackenzie-Kludas, LY Yang Lee, M Wang, H Pointer, K Karavendzas, D Abu-Bonsrah, D Drew, YB Yang Sun, JP Tan, G Sun, A Salavaty, N Charitakis, HT Nim Show all
Stem Cell Reports | CELL PRESS | Published : 2023
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe coronavirus disease 2019 (COVID-19). To elucidate molecular mechanisms in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type II (AT2) epithelial cell and cardiac cultures infected with SARS-CoV-2. With CRISPR-Cas9-mediated knockout of ACE2, we demonstrated that angiotensin-converting enzyme 2 (ACE2) was essential for SARS-CoV-2 infection of both cell types but that further processing in lung cells required TMPRSS2, while cardiac cells required the endosomal pathway. Host responses were sign..
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Grants
Awarded by Royal Children's Hospital Foundation
Funding Acknowledgements
This work was supported by The Medical Research Future Fund (MRF9200007; K.S., E.P., J.M.P., D.A.E.) , the Victorian State Government (Victorian State Government (DJPR/COVID-19; K.S., M.R., E.P., J.M.P., D.A.E.), and the COVID-19 Victorian Consortium (K.S.) . E.P., M.R., and D.A.E. are supported by The Novo Nordisk Foundation Center for Stem Cell Medicine (grant NNF21CC0073729), The Stafford Fox Medical Research Foundation, and The Royal Children's Hospital Foundation. Fellowship support was provided by the National Health and Medical Research Council of Australia (E.P. and K.S.). MCRI is supported by the Victorian Government's Operational Infrastructure Support Program. The Melbourne WHO Collaborating Center for Reference and Research on Influenza is supported by the Australian Government Department of Health.