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Human Cerebral Spheroids Undergo Activity Dependent Changes In Cellular Composition And Microrna Expression

View ORCID ProfileThomas Parmentier, Fiona James, Elizabeth Hewitson, Craig Bailey, Nicholas Werry, Steve D. Sheridan, Roy H. Perlis, Melissa Perreault, Luis Gaitero, View ORCID ProfileJasmin Lalonde, Jonathan LaMarre
doi: https://doi.org/10.1101/2022.02.04.478858
Thomas Parmentier
1Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, CANADA
6T.P. present address is: Département de sciences cliniques, Faculté de médecine vétérinaire, Université de Montréal, Montréal, QC, CANADA
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Fiona James
2Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, CANADA
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Elizabeth Hewitson
1Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, CANADA
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Craig Bailey
1Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, CANADA
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Nicholas Werry
1Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, CANADA
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Steve D. Sheridan
3Center for Quantitative Health, Center for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
4Department of Psychiatry, Harvard Medical School, Boston, MA, USA
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Roy H. Perlis
3Center for Quantitative Health, Center for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
4Department of Psychiatry, Harvard Medical School, Boston, MA, USA
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Melissa Perreault
1Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, CANADA
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Luis Gaitero
2Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, CANADA
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Jasmin Lalonde
5Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, Guelph, ON, CANADA
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Jonathan LaMarre
1Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, CANADA
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  • For correspondence: jlamarre@ovc.uoguelph.ca
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SUMMARY

Activity-induced neurogenesis has been extensively studied in rodents but the lack of ante mortem accessibility to human brain at the cellular and molecular levels limits studies of the process in humans. Using cerebral spheroids derived from human induced pluripotent stem cells (iPSCs), we investigated the effects of increased neuronal activity on neurogenesis. Our studies demonstrate that increasing neuronal activity with 4-aminopyridine in 3-month-old cerebral spheroids is associated with increases in the numbers of new neurons and decreases in the population of new glial cells. We also observed a significant decrease in the expression of miR-135a, which has previously been shown to be decreased in exercise-induced neurogenesis. Predicted targets of miR-135a include key participants in the SMAD2/3 and BDNF pathways. Together, our results suggest that iPSC-derived cerebral spheroids are an attractive model to study some aspects of activity-induced neurogenesis.

Competing Interest Statement

The authors have declared no competing interest.

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Posted February 06, 2022.
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Human Cerebral Spheroids Undergo Activity Dependent Changes In Cellular Composition And Microrna Expression
Thomas Parmentier, Fiona James, Elizabeth Hewitson, Craig Bailey, Nicholas Werry, Steve D. Sheridan, Roy H. Perlis, Melissa Perreault, Luis Gaitero, Jasmin Lalonde, Jonathan LaMarre
bioRxiv 2022.02.04.478858; doi: https://doi.org/10.1101/2022.02.04.478858
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Human Cerebral Spheroids Undergo Activity Dependent Changes In Cellular Composition And Microrna Expression
Thomas Parmentier, Fiona James, Elizabeth Hewitson, Craig Bailey, Nicholas Werry, Steve D. Sheridan, Roy H. Perlis, Melissa Perreault, Luis Gaitero, Jasmin Lalonde, Jonathan LaMarre
bioRxiv 2022.02.04.478858; doi: https://doi.org/10.1101/2022.02.04.478858

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