Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA217985 | ENA |
REPOSITORIES: ENA
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Project description:We performed microarray analyses on human ESCs-derived NPs and neurons carrying loss-of-function mutation in the MeCP2 gene.
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Project description:Human telencephalon is an evolutionary advanced brain structure associated with many uniquely human behaviors and disorders. However, cell lineages and molecular pathways implicated in human telencephalic development remains largely unknown. We generated human telencephalic organoids from stem cell-derived single neural rosettes (SNRs) and investigated telencephalic development under normal and pathological conditions. SNR-derived organoids contained pallial and subpallial neural progenitors (NPs), excitatory and inhibitory neurons, as well as macroglial and periendothelial cells, and demonstrated predictable organization and cytoarchitecture. We comprehensively characterized the properties of neurons in SNR-derived organoids and identified transcriptional programs associated with the specification of+B50:B51 excitatory and inhibitory lineages from a common pool of NPs early in telencephalic development. We also demonstrated that neurons in organoids with a hemizygous deletion of an autism- and intellectual disability associated gene SHANK3 exhibit intrinsic and excitatory synaptic deficits associated with impaired expression of clustered protocadherins. Collectively, this study validates SNR-derived organoids as a reliable new model for studying human telencephalic development and identifies novel molecular pathways disrupted by SHANK3 hemizygosity in human telencephalic tissue.
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