Expression of endogenous angiotensin-converting enzyme 2 in human induced pluripotent stem cell-derived retinal organoids

Henkie Isahwan Ahmad Mulyadi Lai; Shih Jie Chou; Yueh Chien; Ping Hsing Tsai; Chian Shiu Chien; Chih Chien Hsu; Ying Chun Jheng; Mong Lien Wang; Shih Hwa Chiou; Yu Bai Chou; De Kuang Hwang; Tai Chi Lin; Shih Jen Chen; Yi Ping Yang

doi:10.3390/ijms22031320

Expression of endogenous angiotensin-converting enzyme 2 in human induced pluripotent stem cell-derived retinal organoids

Henkie Isahwan Ahmad Mulyadi Lai, Shih Jie Chou, Yueh Chien, Ping Hsing Tsai, Chian Shiu Chien, Chih Chien Hsu, Ying Chun Jheng, Mong Lien Wang, Shih Hwa Chiou, Yu Bai Chou, De Kuang Hwang, Tai Chi Lin^*, Shih Jen Chen, Yi Ping Yang

^*Corresponding author for this work

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

28 Scopus citations

Abstract

Angiotensin-converting enzyme 2 (ACE2) was identified as the main host cell receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent infection. In some coronavirus disease 2019 (COVID-19) patients, it has been reported that the nervous tissues and the eyes were also affected. However, evidence supporting that the retina is a target tissue for SARS-CoV-2 infection is still lacking. This present study aimed to investigate whether ACE2 expression plays a role in human retinal neurons during SARS-CoV-2 infection. Human induced pluripotent stem cell (hiPSC)-derived retinal organoids and monolayer cultures derived from dissociated retinal organoids were generated. To validate the potential entry of SARS-CoV-2 infection in the retina, we showed that hiPSC-derived retinal organoids and monolayer cultures endogenously express ACE2 and transmembrane serine protease 2 (TMPRSS2) on the mRNA level. Immunofluorescence staining confirmed the protein expression of ACE2 and TMPRSS2 in retinal or-ganoids and monolayer cultures. Furthermore, using the SARS-CoV-2 pseudovirus spike protein with GFP expression system, we found that retinal organoids and monolayer cultures can potentially be infected by the SARS-CoV-2 pseudovirus. Collectively, our findings highlighted the potential of iPSC-derived retinal organoids as the models for ACE2 receptor-based SARS-CoV-2 infection.

Original language	English
Article number	1320
Pages (from-to)	1-18
Number of pages	18
Journal	International Journal Of Molecular Sciences
Volume	22
Issue number	3
DOIs	https://doi.org/10.3390/ijms22031320
State	Published - 1 Feb 2021

Keywords

ACE2
COVID-19
Induced pluripotent stem cells
Organoids
SARS-CoV-2
SARS-CoV-2 pseudovirus
Spike protein

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Lai, H. I. A. M., Chou, S. J., Chien, Y., Tsai, P. H., Chien, C. S., Hsu, C. C., Jheng, Y. C., Wang, M. L., Chiou, S. H., Chou, Y. B., Hwang, D. K., Lin, T. C., Chen, S. J., & Yang, Y. P. (2021). Expression of endogenous angiotensin-converting enzyme 2 in human induced pluripotent stem cell-derived retinal organoids. International Journal Of Molecular Sciences, 22(3), 1-18. Article 1320. https://doi.org/10.3390/ijms22031320

@article{af3980d4ce514abd8951666759528a47,

title = "Expression of endogenous angiotensin-converting enzyme 2 in human induced pluripotent stem cell-derived retinal organoids",

abstract = "Angiotensin-converting enzyme 2 (ACE2) was identified as the main host cell receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent infection. In some coronavirus disease 2019 (COVID-19) patients, it has been reported that the nervous tissues and the eyes were also affected. However, evidence supporting that the retina is a target tissue for SARS-CoV-2 infection is still lacking. This present study aimed to investigate whether ACE2 expression plays a role in human retinal neurons during SARS-CoV-2 infection. Human induced pluripotent stem cell (hiPSC)-derived retinal organoids and monolayer cultures derived from dissociated retinal organoids were generated. To validate the potential entry of SARS-CoV-2 infection in the retina, we showed that hiPSC-derived retinal organoids and monolayer cultures endogenously express ACE2 and transmembrane serine protease 2 (TMPRSS2) on the mRNA level. Immunofluorescence staining confirmed the protein expression of ACE2 and TMPRSS2 in retinal or-ganoids and monolayer cultures. Furthermore, using the SARS-CoV-2 pseudovirus spike protein with GFP expression system, we found that retinal organoids and monolayer cultures can potentially be infected by the SARS-CoV-2 pseudovirus. Collectively, our findings highlighted the potential of iPSC-derived retinal organoids as the models for ACE2 receptor-based SARS-CoV-2 infection.",

keywords = "ACE2, COVID-19, Induced pluripotent stem cells, Organoids, SARS-CoV-2, SARS-CoV-2 pseudovirus, Spike protein",

author = "Lai, {Henkie Isahwan Ahmad Mulyadi} and Chou, {Shih Jie} and Yueh Chien and Tsai, {Ping Hsing} and Chien, {Chian Shiu} and Hsu, {Chih Chien} and Jheng, {Ying Chun} and Wang, {Mong Lien} and Chiou, {Shih Hwa} and Chou, {Yu Bai} and Hwang, {De Kuang} and Lin, {Tai Chi} and Chen, {Shih Jen} and Yang, {Yi Ping}",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = feb,

day = "1",

doi = "10.3390/ijms22031320",

language = "English",

volume = "22",

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Lai, HIAM, Chou, SJ, Chien, Y, Tsai, PH, Chien, CS, Hsu, CC, Jheng, YC, Wang, ML, Chiou, SH, Chou, YB, Hwang, DK, Lin, TC, Chen, SJ & Yang, YP 2021, 'Expression of endogenous angiotensin-converting enzyme 2 in human induced pluripotent stem cell-derived retinal organoids', International Journal Of Molecular Sciences, vol. 22, no. 3, 1320, pp. 1-18. https://doi.org/10.3390/ijms22031320

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T1 - Expression of endogenous angiotensin-converting enzyme 2 in human induced pluripotent stem cell-derived retinal organoids

AU - Lai, Henkie Isahwan Ahmad Mulyadi

AU - Chou, Shih Jie

AU - Chien, Yueh

AU - Tsai, Ping Hsing

AU - Chien, Chian Shiu

AU - Hsu, Chih Chien

AU - Jheng, Ying Chun

AU - Wang, Mong Lien

AU - Chiou, Shih Hwa

AU - Chou, Yu Bai

AU - Hwang, De Kuang

AU - Lin, Tai Chi

AU - Chen, Shih Jen

AU - Yang, Yi Ping

PY - 2021/2/1

Y1 - 2021/2/1

N2 - Angiotensin-converting enzyme 2 (ACE2) was identified as the main host cell receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent infection. In some coronavirus disease 2019 (COVID-19) patients, it has been reported that the nervous tissues and the eyes were also affected. However, evidence supporting that the retina is a target tissue for SARS-CoV-2 infection is still lacking. This present study aimed to investigate whether ACE2 expression plays a role in human retinal neurons during SARS-CoV-2 infection. Human induced pluripotent stem cell (hiPSC)-derived retinal organoids and monolayer cultures derived from dissociated retinal organoids were generated. To validate the potential entry of SARS-CoV-2 infection in the retina, we showed that hiPSC-derived retinal organoids and monolayer cultures endogenously express ACE2 and transmembrane serine protease 2 (TMPRSS2) on the mRNA level. Immunofluorescence staining confirmed the protein expression of ACE2 and TMPRSS2 in retinal or-ganoids and monolayer cultures. Furthermore, using the SARS-CoV-2 pseudovirus spike protein with GFP expression system, we found that retinal organoids and monolayer cultures can potentially be infected by the SARS-CoV-2 pseudovirus. Collectively, our findings highlighted the potential of iPSC-derived retinal organoids as the models for ACE2 receptor-based SARS-CoV-2 infection.

AB - Angiotensin-converting enzyme 2 (ACE2) was identified as the main host cell receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent infection. In some coronavirus disease 2019 (COVID-19) patients, it has been reported that the nervous tissues and the eyes were also affected. However, evidence supporting that the retina is a target tissue for SARS-CoV-2 infection is still lacking. This present study aimed to investigate whether ACE2 expression plays a role in human retinal neurons during SARS-CoV-2 infection. Human induced pluripotent stem cell (hiPSC)-derived retinal organoids and monolayer cultures derived from dissociated retinal organoids were generated. To validate the potential entry of SARS-CoV-2 infection in the retina, we showed that hiPSC-derived retinal organoids and monolayer cultures endogenously express ACE2 and transmembrane serine protease 2 (TMPRSS2) on the mRNA level. Immunofluorescence staining confirmed the protein expression of ACE2 and TMPRSS2 in retinal or-ganoids and monolayer cultures. Furthermore, using the SARS-CoV-2 pseudovirus spike protein with GFP expression system, we found that retinal organoids and monolayer cultures can potentially be infected by the SARS-CoV-2 pseudovirus. Collectively, our findings highlighted the potential of iPSC-derived retinal organoids as the models for ACE2 receptor-based SARS-CoV-2 infection.

KW - ACE2

KW - COVID-19

KW - Induced pluripotent stem cells

KW - Organoids

KW - SARS-CoV-2

KW - SARS-CoV-2 pseudovirus

KW - Spike protein

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U2 - 10.3390/ijms22031320

DO - 10.3390/ijms22031320

M3 - Article

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AN - SCOPUS:85099912913

SN - 1661-6596

VL - 22

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JO - International Journal Of Molecular Sciences

JF - International Journal Of Molecular Sciences

IS - 3

M1 - 1320

ER -

Expression of endogenous angiotensin-converting enzyme 2 in human induced pluripotent stem cell-derived retinal organoids

Abstract

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