tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Tae Wan Kim[SUP] 2 [/SUP], Yuling Han[SUP] 1 [/SUP], Manoj S Nair[SUP] 3 [/SUP], Oliver Harschnitz[SUP] 4 [/SUP], Jiajun Zhu[SUP] 1 [/SUP], Pengfei Wang[SUP] 3 [/SUP], So Yeon Koo[SUP] 5 [/SUP], Lauretta A Lacko[SUP] 1 [/SUP], Vasuretha Chandar[SUP] 6 [/SUP], Yaron Bram[SUP] 6 [/SUP], Tuo Zhang[SUP] 7 [/SUP], Wei Zhang[SUP] 8 [/SUP], Feng He[SUP] 7 [/SUP], Chendong Pan[SUP] 7 [/SUP], Junjie Wu[SUP] 1 [/SUP], Yaoxing Huang[SUP] 3 [/SUP], Todd Evans[SUP] 1 [/SUP], Paul van der Valk[SUP] 9 [/SUP], Maarten J Titulaer[SUP] 10 [/SUP], Jochem K H Spoor[SUP] 11 [/SUP], Robert L Furler O'Brien[SUP] 12 [/SUP], Marianna Bugiani[SUP] 13 [/SUP], Wilma D J Van de Berg[SUP] 14 [/SUP], Robert E Schwartz[SUP] 15 [/SUP], David D Ho[SUP] 16 [/SUP], Lorenz Studer[SUP] 17 [/SUP], Shuibing Chen[SUP] 18 [/SUP]
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[SUP] 1 [/SUP], Tae Wan Kim[SUP] 2 [/SUP], Yuling Han[SUP] 1 [/SUP], Manoj S Nair[SUP] 3 [/SUP], Oliver Harschnitz[SUP] 4 [/SUP], Jiajun Zhu[SUP] 1 [/SUP], Pengfei Wang[SUP] 3 [/SUP], So Yeon Koo[SUP] 5 [/SUP], Lauretta A Lacko[SUP] 1 [/SUP], Vasuretha Chandar[SUP] 6 [/SUP], Yaron Bram[SUP] 6 [/SUP], Tuo Zhang[SUP] 7 [/SUP], Wei Zhang[SUP] 8 [/SUP], Feng He[SUP] 7 [/SUP], Chendong Pan[SUP] 7 [/SUP], Junjie Wu[SUP] 1 [/SUP], Yaoxing Huang[SUP] 3 [/SUP], Todd Evans[SUP] 1 [/SUP], Paul van der Valk[SUP] 9 [/SUP], Maarten J Titulaer[SUP] 10 [/SUP], Jochem K H Spoor[SUP] 11 [/SUP], Robert L Furler O'Brien[SUP] 12 [/SUP], Marianna Bugiani[SUP] 13 [/SUP], Wilma D J Van de Berg[SUP] 14 [/SUP], Robert E Schwartz[SUP] 15 [/SUP], David D Ho[SUP] 16 [/SUP], Lorenz Studer[SUP] 17 [/SUP], Shuibing Chen[SUP] 18 [/SUP]
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.