TY - JOUR
T1 - Expression of ACE2 and a viral virulence-regulating factor CCN family member 1 in human iPSC-derived neural cells
T2 - Implications for COVID-19-related CNS disorders
AU - Kase, Yoshitaka
AU - Okano, Hideyuki
N1 - Publisher Copyright:
© 2020 The Author(s).
PY - 2020/9/11
Y1 - 2020/9/11
N2 - It has been reported that coronavirus disease 2019 (COVID-19) causes not only pneumonia but also systemic inflammations including central nervous system (CNS) disorders. However, little is known about the mechanism that triggers the COVID-19-associated CNS disorders, due to the lack of appropriate experimental systems. Our present study showed that angiotensin-converting enzyme-2 (ACE2), a cellular receptor for SARS-CoV-2, is expressed in human induced pluripotent stem cell (iPSC)-derived neural stem/progenitor cells (hiPSC-NS/PCs) and young neurons. Furthermore, together with database analysis, we found that a viral virulent factor CCN family member 1 (CCN1), which is known to be induced by SARS-CoV-2 infection, is expressed in these cells at basal levels. Considering the role of CCN1 which is known to be involved in viral toxicity and inflammation, hiPSC-NS/PCs could provide an excellent model for COVID-19-associated CNS disorders from the aspect of SARS-CoV-2 infection-ACE2-CCN1 axis. In addition, we identified compounds that reduce CCN1 expression. Collectively, our study using hiPSC-NS/PCs may aid in the development of a therapeutic target for COVID-19-related CNS disorders.
AB - It has been reported that coronavirus disease 2019 (COVID-19) causes not only pneumonia but also systemic inflammations including central nervous system (CNS) disorders. However, little is known about the mechanism that triggers the COVID-19-associated CNS disorders, due to the lack of appropriate experimental systems. Our present study showed that angiotensin-converting enzyme-2 (ACE2), a cellular receptor for SARS-CoV-2, is expressed in human induced pluripotent stem cell (iPSC)-derived neural stem/progenitor cells (hiPSC-NS/PCs) and young neurons. Furthermore, together with database analysis, we found that a viral virulent factor CCN family member 1 (CCN1), which is known to be induced by SARS-CoV-2 infection, is expressed in these cells at basal levels. Considering the role of CCN1 which is known to be involved in viral toxicity and inflammation, hiPSC-NS/PCs could provide an excellent model for COVID-19-associated CNS disorders from the aspect of SARS-CoV-2 infection-ACE2-CCN1 axis. In addition, we identified compounds that reduce CCN1 expression. Collectively, our study using hiPSC-NS/PCs may aid in the development of a therapeutic target for COVID-19-related CNS disorders.
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U2 - 10.1186/s41232-020-00143-6
DO - 10.1186/s41232-020-00143-6
M3 - Article
AN - SCOPUS:85091306043
SN - 1880-9693
VL - 40
JO - Inflammation and Regeneration
JF - Inflammation and Regeneration
IS - 1
M1 - 32
ER -
