| First Author | Zheng X | Year | 2024 |
| Journal | Cell | Volume | 187 |
| Issue | 13 | Pages | 3236-3248.e21 |
| PubMed ID | 38772369 | Mgi Jnum | J:349719 |
| Mgi Id | MGI:7658701 | Doi | 10.1016/j.cell.2024.04.050 |
| Citation | Zheng X, et al. (2024) Massively parallel in vivo Perturb-seq reveals cell-type-specific transcriptional networks in cortical development. Cell 187(13):3236-3248.e21 |
| abstractText | Leveraging AAVs' versatile tropism and labeling capacity, we expanded the scale of in vivo CRISPR screening with single-cell transcriptomic phenotyping across embryonic to adult brains and peripheral nervous systems. Through extensive tests of 86 vectors across AAV serotypes combined with a transposon system, we substantially amplified labeling efficacy and accelerated in vivo gene delivery from weeks to days. Our proof-of-principle in utero screen identified the pleiotropic effects of Foxg1, highlighting its tight regulation of distinct networks essential for cell fate specification of Layer 6 corticothalamic neurons. Notably, our platform can label >6% of cerebral cells, surpassing the current state-of-the-art efficacy at <0.1% by lentivirus, to achieve analysis of over 30,000 cells in one experiment and enable massively parallel in vivo Perturb-seq. Compatible with various phenotypic measurements (single-cell or spatial multi-omics), it presents a flexible approach to interrogate gene function across cell types in vivo, translating gene variants to their causal function. |
