Dual genome-wide coding and lncRNA screens in neural induction of induced pluripotent stem cells

David Wu, Aunoy Poddar, Elpiniki Ninou, Elizabeth Hwang, Mitchel A. Cole, S. John Liu, Max A. Horlbeck, Jin Chen, Joseph M. Replogle, Giovanni A. Carosso, Nicolas W.L. Eng, Jonghoon Chang, Yin Shen, Jonathan S. Weissman, Daniel A. Lim

Research output: Contribution to journalArticlepeer-review


Human chromosomes are pervasively transcribed, but systematic understanding of coding and long noncoding RNA (lncRNA) genome function in cell differentiation is lacking. Using CRISPR interference (CRISPRi) in human induced pluripotent stem cells, we performed dual genome-wide screens—assessing 18,905 protein-coding and 10,678 lncRNA loci—and identified 419 coding and 201 lncRNA genes that regulate neural induction. Integrative analyses revealed distinct properties of coding and lncRNA genome function, including a 10-fold enrichment of lncRNA genes for roles in differentiation compared with proliferation. Further, we applied CRISPRi perturbation coupled with single-cell RNA-seq (Perturb-seq) to obtain granular insights into neural induction phenotypes. While most coding hits stalled or aborted differentiation, lncRNA hits were enriched for the genesis of diverse cellular states, including those outside the neural lineage. In addition to providing a rich resource for understanding coding and lncRNA gene function in development, these results indicate that the lncRNA genome regulates lineage commitment in a manner fundamentally distinct from coding genes.

Original languageEnglish (US)
Article number100177
JournalCell Genomics
Issue number11
StatePublished - Nov 9 2022


  • genome-wide pooled screens
  • human pluripotent stem cells
  • iPSCs
  • long noncoding RNA
  • neural induction
  • neurodevelopment
  • Perturb-seq
  • single-cell RNA-seq

ASJC Scopus subject areas

  • Genetics
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)


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