Cerebral organoid proteomics reveals signatures of dysregulated cortical development associated with human trisomy 21

BioRxiv : the Preprint Server for Biology
Tristan D McClure-BegleyWilliam M Old

Abstract

Human trisomy 21 (Down syndrome) is the most common genetic cause of intellectual disability, and is associated with complex perturbations in protein expression during development. Brain region-specific alterations in neuronal density and composition originate prenatally in trisomy 21 individuals, and are presumed to underlie the intellectual disability and early onset neurodegeneration that characterizes Down syndrome. However, the mechanisms by which chromosome 21 aneuploidy drives alterations in the central nervous system are not well understood, particularly in brain regions that are uniquely human and thus inaccessible to established animal models. Cerebral organoids are pluripotent stem cell derived models of prenatal brain development that have been used to deepen our understanding of the atypical processes associated with human neurobiological disorders, and thus provide a promising avenue to explore the molecular basis for neurodevelopmental alterations in trisomy 21. Here, we employ high-resolution label-free mass spectrometry to map proteomic changes over the course of trisomy 21 cerebral organoid development, and evaluate the proteomic alterations in response to treatment with harmine, a small molecule inhibitor of ...Continue Reading

Related Concepts

Brain
Cerebral Cortex
Chromosomes
Chromosomes, Human, Pair 21
Down Syndrome
Extracellular Matrix
Harmine
Nerve Degeneration
Neurons
Organoids

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