SARS-CoV-2 infection of human pluripotent stem cell-derived vascular cells reveals smooth muscle cells as key mediators of vascular pathology during infection

Alexsia Richards, Andrew S. Khalil, Max Friesen, Troy W. Whitfield, Xinlei Gao, Tenzin Lungjangwa, Roger D. Kamm, Zhengpeng Wan, Lee Gehrke, David Mooney () and Rudolf Jaenisch ()
Additional contact information
Alexsia Richards: Whitehead Institute for Biomedical Research
Andrew S. Khalil: Whitehead Institute for Biomedical Research
Max Friesen: Whitehead Institute for Biomedical Research
Troy W. Whitfield: Whitehead Institute for Biomedical Research
Xinlei Gao: Whitehead Institute for Biomedical Research
Tenzin Lungjangwa: Whitehead Institute for Biomedical Research
Roger D. Kamm: Massachusetts Institute of Technology
Zhengpeng Wan: Massachusetts Institute of Technology
Lee Gehrke: Harvard Medical School
David Mooney: Harvard University
Rudolf Jaenisch: Whitehead Institute for Biomedical Research

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), nearly 20% of hospitalized patients are at risk for thromboembolic events. This prothrombotic state is considered a key factor in the increased risk of stroke, which is observed clinically during both acute infection and long after symptoms clear. Here, we develop a model of SARS-CoV-2 infection using human-induced pluripotent stem cell-derived endothelial cells (ECs), pericytes (PCs), and smooth muscle cells (SMCs) to recapitulate the vascular pathology associated with SARS-CoV-2 exposure. Our results demonstrate that perivascular cells, particularly SMCs, are a susceptible vascular target for SARS-CoV-2 infection. Utilizing RNA sequencing, we characterize the transcriptomic changes accompanying SARS-CoV-2 infection of SMCs, PCs, and ECs. We observe that infected SMCs shift to a pro-inflammatory state and increase the expression of key mediators of the coagulation cascade. Further, we show human ECs exposed to the secretome of infected SMCs produce hemostatic factors that contribute to vascular dysfunction despite not being susceptible to direct infection. The findings here recapitulate observations from patient sera in human COVID-19 patients and provide mechanistic insight into the unique vascular implications of SARS-CoV-2 infection at a cellular level.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-54917-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54917-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-54917-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().