A human tissue screen identifies a regulator of ER secretion as a brain-size determinant.
Brain
/ growth & development
CRISPR-Cas Systems
Carrier Proteins
/ genetics
Cell Line
Cell Lineage
Endoplasmic Reticulum
/ metabolism
Extracellular Matrix Proteins
/ metabolism
Gene Knockout Techniques
Genetic Testing
/ methods
Humans
Membrane Proteins
/ genetics
Microcephaly
/ genetics
Organ Size
Organoids
/ growth & development
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
20 11 2020
20 11 2020
Historique:
received:
04
03
2020
accepted:
10
09
2020
pubmed:
31
10
2020
medline:
22
1
2021
entrez:
30
10
2020
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 33122427
pii: science.abb5390
doi: 10.1126/science.abb5390
doi:
Substances chimiques
Carrier Proteins
0
Extracellular Matrix Proteins
0
IER3IP1 protein, human
0
Membrane Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
935-941Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.