![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
| Item Type: | Dataset |
|---|---|
| Title: | Bidirectional editing unveils gene interactions in human brain evolution |
| Creators Name: | Vitriolo, Alessandro and Skaros, Adrianos |
| Abstract: | Comparative genomic studies between contemporary humans and extinct hominins have revealed key evolutionary modifications, but their roles in scaffolding our species’ distinctive traits remain poorly understood. The sheer number of sapiens-specific genetic variants uncovered so far makes it challenging to investigate the mechanisms underlying these recent evolutionary changes at scale. To address this, we developed a scalable gene-editing framework implemented in cortical brain organoids. We prioritized 15 candidate genes among the few carrying nearly fixed protein-coding mutations that distinguish us from other hominins, and developed a CRISPR-Cas9 dual-screen strategy to systematically interrogate the genes’ roles and, above all, their interactions. Combining overexpression and downregulation effects within the same cell, for all possible gene pairs, we mapped the genes’ impacts on single-cell transcriptomic profiles and differentiation potential in cortical brain organoids. We reconstructed the regulatory architecture among genes predicted to have a significant impact on corticogenesis. Pooling all perturbation pairs, we observe marked cell type-specific effects, alternative cell fates favoring neurons or glia, as well as the timing of emergence of interneuron populations. A core subnetwork made up of KIF15, NOVA1, RB1CC1 and SPAG5 was found to be a central regulator across cortex cell types. |
| Source: | Zenodo |
| Publisher: | CERN |
| Date: | 31 December 2025 |
| Official Publication: | https://doi.org/10.5281/zenodo.15026303 |
Repository Staff Only: item control page
