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

doi:10.1126/science.abb5390

GSTDTAP > 气候变化

DOI	10.1126/science.abb5390
	A human tissue screen identifies a regulator of ER secretion as a brain-size determinant
	Christopher Esk; Dominik Lindenhofer; Simon Haendeler; Roelof A. Wester; Florian Pflug; Benoit Schroeder; Joshua A. Bagley; Ulrich Elling; Johannes Zuber; Arndt von Haeseler; Jürgen A. Knoblich
	2020-11-20
发表期刊	Science
出版年	2020
英文摘要	Genetic screens are widely used to identify regulators in biological processes. Human screens are currently limited to two-dimensional cell cultures, which lack the ability to score tissue-dependent gene function. Esk et al. combined CRISPR-Cas9 screening with barcoded cellular lineage tracing to enable loss-of-function screening in three-dimensional human cerebral organoid tissue. By testing microcephaly candidate genes, the endoplasmic reticulum was found to control extracellular matrix protein secretion regulating tissue integrity and brain size. This genetic screen in human brain tissue implicates multiple pathways in microcephaly and provides a tool for systematic testing of genes in organoids. Science , this issue p. [935][1] 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 cell cultures, which hinders the testing of gene functions requiring tissue context. Here, we present CRISPR–lineage tracing at cellular resolution in heterogeneous tissue (CRISPR-LICHT), which enables 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 IER3IP1 , which regulates the endoplasmic reticulum (ER) function and extracellular matrix protein secretion crucial for tissue integrity, the dysregulation of which results in microcephaly. Our human tissue screening technology identifies microcephaly genes and mechanisms involved in brain-size control. [1]: /lookup/doi/10.1126/science.abb5390
领域	气候变化 ; 资源环境
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引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/304399
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Christopher Esk,Dominik Lindenhofer,Simon Haendeler,et al. A human tissue screen identifies a regulator of ER secretion as a brain-size determinant[J]. Science,2020.
APA	Christopher Esk.,Dominik Lindenhofer.,Simon Haendeler.,Roelof A. Wester.,Florian Pflug.,...&Jürgen A. Knoblich.(2020).A human tissue screen identifies a regulator of ER secretion as a brain-size determinant.Science.
MLA	Christopher Esk,et al."A human tissue screen identifies a regulator of ER secretion as a brain-size determinant".Science (2020).