ArticleStem cell reports2023
Optimized whole-genome CRISPR interference screens identify ARID1A-dependent growth regulators in human induced pluripotent stem cells.
Article in Stem cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 14 citations in OpenAlex.
- Programmable CRISPRtune dissects the transcriptional repressive activity of MeCP2.bioRxiv : the preprint server for biology · 2026Article
- High genotoxicity of CRISPR/Cas9 versus limited efficacy of CRISPRi in chicken primordial germ cells.Poultry science · 2026Article
- A robust cis-regulatory network ensures Otx2 expression during retinal development.Development (Cambridge, England) · 2026Article
- A genome-scale single-cell CRISPRi map of trans gene regulation across human pluripotent stem cell lines.Cell genomics · 2026Article
- CRISPR/Cas-mediated mRNA knockdown in the embryos of Xenopus tropicalis.Cell & bioscience · 2025Article
- CRISPRi: a way to integrate iPSC-derived neuronal models.Biochemical Society transactions · 2024Review
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Perturbing expression is a powerful way to understand the role of individual genes, but can be challenging in important models. CRISPR-Cas screens in human induced pluripotent stem cells (iPSCs) are of limited efficiency due to DNA break-induced stress, while the less stressful silencing with an inactive Cas9 has been considered less effective so far. Here, we developed the dCas9-KRAB-MeCP2 fusion protein for screening in iPSCs from multiple donors. We found silencing in a 200 bp window around the transcription start site in polyclonal pools to be as effective as using wild-type Cas9 for identifying essential genes, but with much reduced cell numbers. Whole-genome screens to identify ARID1A-dependent dosage sensitivity revealed the PSMB2 gene, and enrichment of proteasome genes among the hits. This selective dependency was replicated with a proteasome inhibitor, indicating a targetable drug-gene interaction. Many more plausible targets in challenging cell models can be efficiently identified with our approach.
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Registered trials
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