Glial cell diversity and methamphetamine-induced neuroinflammation in human cerebral organoids
| Autor: | Jason Dang, Yue Qin, Shashi Kant Tiwari, Kriti Agrawal, Tariq M. Rana, Hui Hui |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Programmed cell death Cell type Biology neural stem cell differentiation Medical and Health Sciences Article neuroinflammation Methamphetamine 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation 3D organoids Organoid Humans Molecular Biology Neuroinflammation Neurons Psychiatry single-cell RNA-seq neural cells Psychology and Cognitive Sciences Meth Biological Sciences Embryonic stem cell cytokines Neural stem cell glial cells Cell biology Organoids Psychiatry and Mental health 030104 developmental biology chemistry Astrocytes Central Nervous System Stimulants 030217 neurology & neurosurgery |
| Zdroj: | Molecular psychiatry, vol 26, iss 4 Molecular psychiatry |
| Popis: | Methamphetamine (METH) is a potent stimulant that induces a euphoric state but also causes cognitive impairment, neurotoxicity and neurodevelopmental deficits. Yet, the molecular mechanisms by which METH causes neurodevelopmental defects have remained elusive. Here we utilized human cerebral organoids and single-cell RNA sequencing (scRNA-seq) to study the effects of prenatal METH exposure on fetal brain development. We analyzed 20,758 cells from eight untreated and six METH-treated cerebral organoids and found that the organoids developed from embryonic stem cells contained a diverse array of glial and neuronal cell types. We further identified transcriptionally distinct populations of astrocytes and oligodendrocytes within cerebral organoids. Treatment of organoids with METH-induced marked changes in transcription in multiple cell types, including astrocytes and neural progenitor cells. METH also elicited novel astrocyte-specific gene expression networks regulating responses to cytokines, and inflammasome. Moreover, upregulation of immediate early genes, complement factors, apoptosis, and immune response genes suggests a neuroinflammatory program induced by METH regulating neural stem cell proliferation, differentiation, and cell death. Finally, we observed marked METH-induced changes in neuroinflammatory and cytokine gene expression at the RNA and protein levels. Our data suggest that human cerebral organoids represent a model system to study drug-induced neuroinflammation at single-cell resolution. |
| Databáze: | OpenAIRE |
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