RT Journal Article
SR Electronic
T1 Genome-wide screens in accelerated human stem cell-derived neural progenitor cells identify Zika virus host factors and drivers of proliferation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 476440
DO 10.1101/476440
A1 Michael F. Wells
A1 Max R. Salick
A1 Federica Piccioni
A1 Ellen J. Hill
A1 Jana M. Mitchell
A1 Kathleen A. Worringer
A1 Joseph J. Raymond
A1 Sravya Kommineni
A1 Karrie Chan
A1 Daniel Ho
A1 Brant K. Peterson
A1 Marco T. Siekmann
A1 Olli Pietilainen
A1 Ralda Nehme
A1 Ajamete Kaykas
A1 Kevin Eggan
YR 2018
UL http://biorxiv.org/content/early/2018/11/22/476440.abstract
AB Neural progenitor cells (NPCs) are essential to brain development and their dysfunction is linked to several disorders, including autism, Zika Virus Congenital Syndrome, and cancer. Understanding of these conditions has been improved by advancements with stem cell-derived NPC models. However, current differentiation methods require many days or weeks to generate NPCs and show variability in efficacy among cell lines. Here, we describe human Stem cell-derived NGN2-accelerated Progenitor cells (SNaPs), which are produced in only 48 hours. SNaPs express canonical forebrain NPC protein markers, are proliferative, multipotent, and like other human NPCs, are susceptible to Zika-mediated death. We further demonstrate SNaPs are valuable for large-scale investigations of genetic and environmental influencers of neurodevelopment by deploying them for genome-wide CRISPR-Cas9 screens. Our studies expand knowledge of NPCs by identifying known and novel Zika host factors, as well as new regulators of NPC proliferation validated by re-identification of the autism spectrum gene PTEN.