奥地利科学院Jürgen A. Knoblich研究团队利用人类组织筛选新技术鉴定出一个ER分泌调控因子参与大脑尺寸决定。相关论文于2020年10月29日在线发表在《科学》杂志上。

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

Author: 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

Issue&Volume: 2020/10/29

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.

DOI: 10.1126/science.abb5390

Source: https://science.sciencemag.org/content/early/2020/10/28/science.abb5390