Investigating microglia-neuron crosstalk by characterizing microglial contamination in human and mouse patch-seq datasets
Summary: Microglia are cells with diverse roles, including the regulation of neuronal excitability. We leveraged Patch-seq to assess the presence and effects of microglia in the local microenvironment of recorded neurons. We first quantified the amounts of microglial transcripts in three Patch-seq d...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223014062 |
| _version_ | 1827894554601193472 |
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| author | Keon Arbabi Yiyue Jiang Derek Howard Anukrati Nigam Wataru Inoue Guillermo Gonzalez-Burgos Daniel Felsky Shreejoy J. Tripathy |
| author_facet | Keon Arbabi Yiyue Jiang Derek Howard Anukrati Nigam Wataru Inoue Guillermo Gonzalez-Burgos Daniel Felsky Shreejoy J. Tripathy |
| author_sort | Keon Arbabi |
| collection | DOAJ |
| description | Summary: Microglia are cells with diverse roles, including the regulation of neuronal excitability. We leveraged Patch-seq to assess the presence and effects of microglia in the local microenvironment of recorded neurons. We first quantified the amounts of microglial transcripts in three Patch-seq datasets of human and mouse neocortical neurons, observing extensive contamination. Variation in microglial contamination was explained foremost by donor identity, particularly in human samples, and additionally by neuronal cell type identity in mice. Gene set enrichment analysis suggests that microglial contamination is reflective of activated microglia, and that these transcriptional signatures are distinct from those captured via single-nucleus RNA-seq. Finally, neurons with greater microglial contamination differed markedly in their electrophysiological characteristics, including lowered input resistances and more depolarized action potential thresholds. Our results generalize beyond Patch-seq to suggest that activated microglia may be widely present across brain slice preparations and contribute to neuron- and donor-related electrophysiological variability in vitro. |
| first_indexed | 2024-03-12T22:09:01Z |
| format | Article |
| id | doaj.art-5ef8c99d6bcf4b1d979c6859ba7920fc |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T22:09:01Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-5ef8c99d6bcf4b1d979c6859ba7920fc2023-07-24T04:10:48ZengElsevieriScience2589-00422023-08-01268107329Investigating microglia-neuron crosstalk by characterizing microglial contamination in human and mouse patch-seq datasetsKeon Arbabi0Yiyue Jiang1Derek Howard2Anukrati Nigam3Wataru Inoue4Guillermo Gonzalez-Burgos5Daniel Felsky6Shreejoy J. Tripathy7The Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, CanadaThe Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, CanadaThe Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, CanadaThe Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, CanadaRobarts Research Institute, Western University, London, Canada; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, CanadaTranslational Neuroscience Program, Department of Psychiatry, University of Pittsburgh, 3811 O’Hara Street, Pittsburgh, PA 15213, USAThe Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, CanadaThe Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada; Corresponding authorSummary: Microglia are cells with diverse roles, including the regulation of neuronal excitability. We leveraged Patch-seq to assess the presence and effects of microglia in the local microenvironment of recorded neurons. We first quantified the amounts of microglial transcripts in three Patch-seq datasets of human and mouse neocortical neurons, observing extensive contamination. Variation in microglial contamination was explained foremost by donor identity, particularly in human samples, and additionally by neuronal cell type identity in mice. Gene set enrichment analysis suggests that microglial contamination is reflective of activated microglia, and that these transcriptional signatures are distinct from those captured via single-nucleus RNA-seq. Finally, neurons with greater microglial contamination differed markedly in their electrophysiological characteristics, including lowered input resistances and more depolarized action potential thresholds. Our results generalize beyond Patch-seq to suggest that activated microglia may be widely present across brain slice preparations and contribute to neuron- and donor-related electrophysiological variability in vitro.http://www.sciencedirect.com/science/article/pii/S2589004223014062Cellular neuroscienceTechniques in neuroscienceTranscriptomics |
| spellingShingle | Keon Arbabi Yiyue Jiang Derek Howard Anukrati Nigam Wataru Inoue Guillermo Gonzalez-Burgos Daniel Felsky Shreejoy J. Tripathy Investigating microglia-neuron crosstalk by characterizing microglial contamination in human and mouse patch-seq datasets iScience Cellular neuroscience Techniques in neuroscience Transcriptomics |
| title | Investigating microglia-neuron crosstalk by characterizing microglial contamination in human and mouse patch-seq datasets |
| title_full | Investigating microglia-neuron crosstalk by characterizing microglial contamination in human and mouse patch-seq datasets |
| title_fullStr | Investigating microglia-neuron crosstalk by characterizing microglial contamination in human and mouse patch-seq datasets |
| title_full_unstemmed | Investigating microglia-neuron crosstalk by characterizing microglial contamination in human and mouse patch-seq datasets |
| title_short | Investigating microglia-neuron crosstalk by characterizing microglial contamination in human and mouse patch-seq datasets |
| title_sort | investigating microglia neuron crosstalk by characterizing microglial contamination in human and mouse patch seq datasets |
| topic | Cellular neuroscience Techniques in neuroscience Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223014062 |
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