Expression of ACE2 and a viral virulence-regulating factor CCN family member 1 in human iPSC-derived neural cells: impli
- PDF / 2,963,733 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 23 Downloads / 151 Views
(2020) 40:32
Inflammation and Regeneration
RAPID COMMUNICATION
Open Access
Expression of ACE2 and a viral virulenceregulating factor CCN family member 1 in human iPSC-derived neural cells: implications for COVID-19-related CNS disorders Yoshitaka Kase1,2 and Hideyuki Okano1*
Abstract 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-ACE2CCN1 axis. In addition, we identified compounds that reduce CCN1 expression. Collectively, our study using hiPSCNS/PCs may aid in the development of a therapeutic target for COVID-19-related CNS disorders. Keywords: ACE2, CCN1 (Cyr61), CNS disorder, COVID-19, hiPSC-NS/PCs, SARS-CoV-2
Background Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is spreading worldwide at the largest scale and fastest speed [1]. As of June 2020, the cumulative number of infected people was more than 9.6 million, with more than 490,000 deaths due to coronavirus disease 2019 (COVID19) [2]. SARS-CoV-2-infected cells which express angiotensin-converting enzyme-2 (ACE2) and TMPRSS2 [3, 4]. ACE2 is expressed in epithelial cells of the oral mucosa [5], respiratory tract including the lungs [4], and digestive tract [6]. The virus specifically infects these cells with strong * Correspondence: [email protected] 1 Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan Full list of author information is available at the end of the article
toxicity, which causes various symptoms, such as pneumonia, diarrhea, and taste and olfactory dysfunction. Furthermore, COVID-19 has been reported to cause various dysfunctions of the central nervous system (CNS) [7]. Coronaviruses other than SARS-CoV-2 are known to have neuroinvasive capacities, entering the CNS from the respiratory tract [8]. In addition, it has been reported that patients with severe COVID-19 are more susceptible to CNS disorders than those with non-severe disease [7]. A previous study found that patients, especially those with high-risk factors such as older age and comorbidities (e.g., hypertension) [7], developed not only mild symptoms but also life-threatening com
Data Loading...
