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| Item Type: | Article |
|---|---|
| Title: | Sensitive dissection of a genomic regulatory landscape using bulk and targeted single-cell activation |
| Creators Name: | Vučićević, Dubravka, Hsu, Che-Wei, Lopez Zepeda, Lorena Sofia, Burkert, Martin, Hirsekorn, Antje, Bilić, Ilija, Kastelić, Nicolai, Landthaler, Markus, Lacadie, Scott Allen and Ohler, Uwe |
| Abstract: | Enhancers are known to spatiotemporally regulate gene transcription, yet the identification of enhancers and their target genes is often indirect, low resolution, and/or assumptive. To identify and functionally perturb enhancers at their endogenous sites, we performed a pooled tiling CRISPR activation (CRISPRa) screen surrounding PHOX2B, a master regulator of neuronal cell fate and a key player in neuroblastoma, and found many CRISPRa-responsive elements (CaREs) that alter cellular growth. To determine CaRE target genes, we developed TESLA-seq (targeted single-cell activation), which combines CRISPRa screening with targeted single-cell RNA sequencing and enables the parallel readout of the effect of hundreds of enhancers on all genes in the locus. While most TESLA-revealed CaRE-gene relationships involved neuroblastoma-related regulatory elements, we found many CaREs and target connections normally active only in other tissues. This highlights the power of TESLA-seq to reveal gene regulatory networks, including edges active outside of a given experimental system. |
| Keywords: | CRISPR Screen, CRISPRa, Targeted scRNA-seq, TESLA-seq, PHOX2B, SHISA3, Enhancers, Transcription, Single-Cell Genomics |
| Source: | Cell Genomics |
| ISSN: | 2666-979X |
| Publisher: | Cell Press |
| Page Range: | 100984 |
| Date: | 9 September 2025 |
| Official Publication: | https://doi.org/10.1016/j.xgen.2025.100984 |
| PubMed: | View item in PubMed |
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