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Cell Stem Cell
. 2024 Jan 10:S1934-5909(23)00442-3.
doi: 10.1016/j.stem.2023.12.012. Online ahead of print. SARS-CoV-2 infection causes dopaminergic neuron senescence
Liuliu Yang 1 , Tae Wan Kim 2 , Yuling Han 1 , Manoj S Nair 3 , Oliver Harschnitz 4 , Jiajun Zhu 1 , Pengfei Wang 3 , So Yeon Koo 5 , Lauretta A Lacko 1 , Vasuretha Chandar 6 , Yaron Bram 6 , Tuo Zhang 7 , Wei Zhang 8 , Feng He 7 , Chendong Pan 7 , Junjie Wu 1 , Yaoxing Huang 3 , Todd Evans 1 , Paul van der Valk 9 , Maarten J Titulaer 10 , Jochem K H Spoor 11 , Robert L Furler O'Brien 12 , Marianna Bugiani 13 , Wilma D J Van de Berg 14 , Robert E Schwartz 15 , David D Ho 16 , Lorenz Studer 17 , Shuibing Chen 18
Affiliations
COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.
Keywords: SARS-CoV-2; dopaminergic neuron; human pluripotent stem cells; senescence.
. 2024 Jan 10:S1934-5909(23)00442-3.
doi: 10.1016/j.stem.2023.12.012. Online ahead of print. SARS-CoV-2 infection causes dopaminergic neuron senescence
Liuliu Yang 1 , Tae Wan Kim 2 , Yuling Han 1 , Manoj S Nair 3 , Oliver Harschnitz 4 , Jiajun Zhu 1 , Pengfei Wang 3 , So Yeon Koo 5 , Lauretta A Lacko 1 , Vasuretha Chandar 6 , Yaron Bram 6 , Tuo Zhang 7 , Wei Zhang 8 , Feng He 7 , Chendong Pan 7 , Junjie Wu 1 , Yaoxing Huang 3 , Todd Evans 1 , Paul van der Valk 9 , Maarten J Titulaer 10 , Jochem K H Spoor 11 , Robert L Furler O'Brien 12 , Marianna Bugiani 13 , Wilma D J Van de Berg 14 , Robert E Schwartz 15 , David D Ho 16 , Lorenz Studer 17 , Shuibing Chen 18
Affiliations
- PMID: 38237586
- DOI: 10.1016/j.stem.2023.12.012
COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.
Keywords: SARS-CoV-2; dopaminergic neuron; human pluripotent stem cells; senescence.