2021
DOI: 10.1038/s41593-021-00923-4
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Human ALS/FTD brain organoid slice cultures display distinct early astrocyte and targetable neuronal pathology

Abstract: Amyotrophic lateral sclerosis overlapping with frontotemporal dementia (ALS/FTD) is a fatal and currently untreatable disease characterized by rapid cognitive decline and paralysis. Elucidating initial cellular pathologies is central to therapeutic target development, but obtaining samples from presymptomatic patients is not feasible. Here, we report the development of a cerebral organoid slice model derived from human induced pluripotent stem cells (iPSCs) that recapitulates mature cortical architecture and d… Show more

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Cited by 110 publications
(84 citation statements)
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References 70 publications
(113 reference statements)
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“…These methods summarize the different steps of human cortical development, such as neurogenesis, gene expression profile, and regional and layer organization [172], and new protocols to produce myelinating oligodendrocytes, cortical neurons, and astrocytes have been recently released [173]. Organoids have successfully modeled CNS disorders, such as autosomal recessive primary microcephaly, brain infection by Zika virus, prenatal cocaine or nicotine exposure, or neonatal hypoxic stress [174], or recently traumatic brain injury [175] or ALS overlapping with frontotemporal dementia [176].…”
Section: Challenges and Perspectivesmentioning
confidence: 99%
“…These methods summarize the different steps of human cortical development, such as neurogenesis, gene expression profile, and regional and layer organization [172], and new protocols to produce myelinating oligodendrocytes, cortical neurons, and astrocytes have been recently released [173]. Organoids have successfully modeled CNS disorders, such as autosomal recessive primary microcephaly, brain infection by Zika virus, prenatal cocaine or nicotine exposure, or neonatal hypoxic stress [174], or recently traumatic brain injury [175] or ALS overlapping with frontotemporal dementia [176].…”
Section: Challenges and Perspectivesmentioning
confidence: 99%
“…While the approach is valid and can provide a view of the network activity of the culture, the full benefit of having a 3D model is not achieved as the MEA can only provide data from a single 2D plane. It is also possible to slice an organoid for the recordings ( Figure 2 ) [ 208 , 209 , 210 ] but this is hardly helpful if the goal is to study an intact 3D network from multiple 2D planes. Furthermore, slicing a small organoid and handling the delicate slices ( Figure 2 ) requires specific protocols that include embedding the organoid in an agarose block for slicing and applying sufficient recovery periods before recording.…”
Section: Hpsc-derived 3d Neuronal Cultures and Organoids On Measmentioning
confidence: 99%
“…Furthermore, slicing a small organoid and handling the delicate slices ( Figure 2 ) requires specific protocols that include embedding the organoid in an agarose block for slicing and applying sufficient recovery periods before recording. The electrodes of certain arrays do penetrate the sample [ 69 , 208 , 210 ] ( Figure 2 ), which in itself is a distinct advantage as the dead cell layer on the surface of the sliced sample is overcome, but measurements are still made only from a single 2D plane.…”
Section: Hpsc-derived 3d Neuronal Cultures and Organoids On Measmentioning
confidence: 99%
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