The SARS-CoV-2 receptor ACE2 is expressed in mouse pericytes but not endothelial cells: Implications for COVID-19 vascular research

Lars Muhl; Liqun He; Ying Sun; Maarja Andaloussi Mäe; Riikka Pietilä; Jianping Liu; Guillem Genové; Lei Zhang; Yuan Xie; Stefanos Leptidis; Giuseppe Mocci; Simon Stritt; Ahmed Osman; Andrey Anisimov; Karthik Amudhala Hemanthakumar; Markus Räsänen; Emil M. Hansson; Johan Björkegren; Michael Vanlandewijck; Klas Blomgren; Taija Mäkinen; Xiao Rong Peng; Yizhou Hu; Patrik Ernfors; Thomas D. Arnold; Kari Alitalo; Urban Lendahl; Christer Betsholtz

doi:10.1016/j.stemcr.2022.03.016

The SARS-CoV-2 receptor ACE2 is expressed in mouse pericytes but not endothelial cells: Implications for COVID-19 vascular research

Lars Muhl, Liqun He, Ying Sun, Maarja Andaloussi Mäe, Riikka Pietilä, Jianping Liu, Guillem Genové, Lei Zhang, Yuan Xie, Stefanos Leptidis, Giuseppe Mocci, Simon Stritt, Ahmed Osman, Andrey Anisimov, Karthik Amudhala Hemanthakumar, Markus Räsänen, Emil M. Hansson, Johan Björkegren, Michael Vanlandewijck, Klas BlomgrenTaija Mäkinen, Xiao Rong Peng, Yizhou Hu, Patrik Ernfors, Thomas D. Arnold, Kari Alitalo, Urban Lendahl, Christer Betsholtz

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

Humanized mouse models and mouse-adapted SARS-CoV-2 virus are increasingly used to study COVID-19 pathogenesis, so it is important to learn where the SARS-CoV-2 receptor ACE2 is expressed. Here we mapped ACE2 expression during mouse postnatal development and in adulthood. Pericytes in the CNS, heart, and pancreas express ACE2 strongly, as do perineurial and adrenal fibroblasts, whereas endothelial cells do not at any location analyzed. In a number of other organs, pericytes do not express ACE2, including in the lung where ACE2 instead is expressed in bronchial epithelium and alveolar type II cells. The onset of ACE2 expression is organ specific: in bronchial epithelium already at birth, in brain pericytes before, and in heart pericytes after postnatal day 10.5. Establishing the vascular localization of ACE2 expression is central to correctly interpret data from modeling COVID-19 in the mouse and may shed light on the cause of vascular COVID-19 complications.

Original language	English
Pages (from-to)	1089-1104
Number of pages	16
Journal	Stem Cell Reports
Volume	17
Issue number	5
DOIs	https://doi.org/10.1016/j.stemcr.2022.03.016
State	Published - 10 May 2022

Keywords

Angiotensin converting enzyme 2 (ACE2)
COVID-19
Endothelial Cells
SARS-CoV-2
Vasculature
pericytes
single-cell RNA-sequencing

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10.1016/j.stemcr.2022.03.016

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Muhl, L., He, L., Sun, Y., Andaloussi Mäe, M., Pietilä, R., Liu, J., Genové, G., Zhang, L., Xie, Y., Leptidis, S., Mocci, G., Stritt, S., Osman, A., Anisimov, A., Hemanthakumar, K. A., Räsänen, M., Hansson, E. M., Björkegren, J., Vanlandewijck, M., ... Betsholtz, C. (2022). The SARS-CoV-2 receptor ACE2 is expressed in mouse pericytes but not endothelial cells: Implications for COVID-19 vascular research. Stem Cell Reports, 17(5), 1089-1104. https://doi.org/10.1016/j.stemcr.2022.03.016

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title = "The SARS-CoV-2 receptor ACE2 is expressed in mouse pericytes but not endothelial cells: Implications for COVID-19 vascular research",

abstract = "Humanized mouse models and mouse-adapted SARS-CoV-2 virus are increasingly used to study COVID-19 pathogenesis, so it is important to learn where the SARS-CoV-2 receptor ACE2 is expressed. Here we mapped ACE2 expression during mouse postnatal development and in adulthood. Pericytes in the CNS, heart, and pancreas express ACE2 strongly, as do perineurial and adrenal fibroblasts, whereas endothelial cells do not at any location analyzed. In a number of other organs, pericytes do not express ACE2, including in the lung where ACE2 instead is expressed in bronchial epithelium and alveolar type II cells. The onset of ACE2 expression is organ specific: in bronchial epithelium already at birth, in brain pericytes before, and in heart pericytes after postnatal day 10.5. Establishing the vascular localization of ACE2 expression is central to correctly interpret data from modeling COVID-19 in the mouse and may shed light on the cause of vascular COVID-19 complications.",

keywords = "Angiotensin converting enzyme 2 (ACE2), COVID-19, Endothelial Cells, SARS-CoV-2, Vasculature, pericytes, single-cell RNA-sequencing",

author = "Lars Muhl and Liqun He and Ying Sun and {Andaloussi M{\"a}e}, Maarja and Riikka Pietil{\"a} and Jianping Liu and Guillem Genov{\'e} and Lei Zhang and Yuan Xie and Stefanos Leptidis and Giuseppe Mocci and Simon Stritt and Ahmed Osman and Andrey Anisimov and Hemanthakumar, {Karthik Amudhala} and Markus R{\"a}s{\"a}nen and Hansson, {Emil M.} and Johan Bj{\"o}rkegren and Michael Vanlandewijck and Klas Blomgren and Taija M{\"a}kinen and Peng, {Xiao Rong} and Yizhou Hu and Patrik Ernfors and Arnold, {Thomas D.} and Kari Alitalo and Urban Lendahl and Christer Betsholtz",

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month = may,

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doi = "10.1016/j.stemcr.2022.03.016",

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Muhl, L, He, L, Sun, Y, Andaloussi Mäe, M, Pietilä, R, Liu, J, Genové, G, Zhang, L, Xie, Y, Leptidis, S, Mocci, G, Stritt, S, Osman, A, Anisimov, A, Hemanthakumar, KA, Räsänen, M, Hansson, EM, Björkegren, J, Vanlandewijck, M, Blomgren, K, Mäkinen, T, Peng, XR, Hu, Y, Ernfors, P, Arnold, TD, Alitalo, K, Lendahl, U & Betsholtz, C 2022, 'The SARS-CoV-2 receptor ACE2 is expressed in mouse pericytes but not endothelial cells: Implications for COVID-19 vascular research', Stem Cell Reports, vol. 17, no. 5, pp. 1089-1104. https://doi.org/10.1016/j.stemcr.2022.03.016

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T1 - The SARS-CoV-2 receptor ACE2 is expressed in mouse pericytes but not endothelial cells

T2 - Implications for COVID-19 vascular research

AU - Muhl, Lars

AU - He, Liqun

AU - Sun, Ying

AU - Andaloussi Mäe, Maarja

AU - Pietilä, Riikka

AU - Liu, Jianping

AU - Genové, Guillem

AU - Zhang, Lei

AU - Xie, Yuan

AU - Leptidis, Stefanos

AU - Mocci, Giuseppe

AU - Stritt, Simon

AU - Osman, Ahmed

AU - Anisimov, Andrey

AU - Hemanthakumar, Karthik Amudhala

AU - Räsänen, Markus

AU - Hansson, Emil M.

AU - Björkegren, Johan

AU - Vanlandewijck, Michael

AU - Blomgren, Klas

AU - Mäkinen, Taija

AU - Peng, Xiao Rong

AU - Hu, Yizhou

AU - Ernfors, Patrik

AU - Arnold, Thomas D.

AU - Alitalo, Kari

AU - Lendahl, Urban

AU - Betsholtz, Christer

PY - 2022/5/10

Y1 - 2022/5/10

N2 - Humanized mouse models and mouse-adapted SARS-CoV-2 virus are increasingly used to study COVID-19 pathogenesis, so it is important to learn where the SARS-CoV-2 receptor ACE2 is expressed. Here we mapped ACE2 expression during mouse postnatal development and in adulthood. Pericytes in the CNS, heart, and pancreas express ACE2 strongly, as do perineurial and adrenal fibroblasts, whereas endothelial cells do not at any location analyzed. In a number of other organs, pericytes do not express ACE2, including in the lung where ACE2 instead is expressed in bronchial epithelium and alveolar type II cells. The onset of ACE2 expression is organ specific: in bronchial epithelium already at birth, in brain pericytes before, and in heart pericytes after postnatal day 10.5. Establishing the vascular localization of ACE2 expression is central to correctly interpret data from modeling COVID-19 in the mouse and may shed light on the cause of vascular COVID-19 complications.

AB - Humanized mouse models and mouse-adapted SARS-CoV-2 virus are increasingly used to study COVID-19 pathogenesis, so it is important to learn where the SARS-CoV-2 receptor ACE2 is expressed. Here we mapped ACE2 expression during mouse postnatal development and in adulthood. Pericytes in the CNS, heart, and pancreas express ACE2 strongly, as do perineurial and adrenal fibroblasts, whereas endothelial cells do not at any location analyzed. In a number of other organs, pericytes do not express ACE2, including in the lung where ACE2 instead is expressed in bronchial epithelium and alveolar type II cells. The onset of ACE2 expression is organ specific: in bronchial epithelium already at birth, in brain pericytes before, and in heart pericytes after postnatal day 10.5. Establishing the vascular localization of ACE2 expression is central to correctly interpret data from modeling COVID-19 in the mouse and may shed light on the cause of vascular COVID-19 complications.

KW - Angiotensin converting enzyme 2 (ACE2)

KW - COVID-19

KW - Endothelial Cells

KW - SARS-CoV-2

KW - Vasculature

KW - pericytes

KW - single-cell RNA-sequencing

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DO - 10.1016/j.stemcr.2022.03.016

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SN - 2213-6711

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JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 5

ER -

The SARS-CoV-2 receptor ACE2 is expressed in mouse pericytes but not endothelial cells: Implications for COVID-19 vascular research

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Keywords

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