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A human tissue screen identifies a regulator of ER secretion as a brain size determinant [organoid - lineage tracing]

ABSTRACT: A screen in human organoids reveals IER3IP1 function

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE151383 | GEO | 2020/11/01

REPOSITORIES: GEO

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A human tissue screen identifies a regulator of ER secretion as a brain size determinant [organoid - screen]

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Project description:A human tissue screen identifies a regulator of ER secretion as a brain size determinant. Abstract: Loss-of-function (LOF) screens provide a powerful approach to identify regulators in biological processes. Pioneered in laboratory animals, LOF screens of human genes are currently restricted to two-dimensional (2D) cell culture hindering testing of gene functions requiring tissue context. Here we present CRISPR-LIneage tracing at Cellular resolution in Heterogenous Tissue (CRISPR-LICHT), enabling parallel LOF studies in human cerebral organoid tissue. We used CRISPR-LICHT to test 173 microcephaly candidate genes revealing 25 to be involved in known and uncharacterized microcephaly-associated pathways. We characterized Immediate Early Response 3 Interacting Protein 1 (IER3IP1) regulating the unfolded protein response (UPR) and extracellular matrix (ECM) protein secretion crucial for tissue integrity, with dysregulation resulting in microcephaly. Our human tissue screening technology identifies microcephaly genes and mechanisms involved in brain size control.

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