Transcript-guided targeted cell enrichment for scalable single-nucleus RNA sequencing.
| Publication Type | Academic Article |
| Authors | Liao A, Zhang Z, Sziraki A, Abdulraouf A, Rehman A, Xu Z, Lu Z, Jiang W, Arya A, Lee J, Maragkakis M, Zhou W, Cao J |
| Journal | Cell Genom |
| Pagination | 101101 |
| Date Published | 12/11/2025 |
| ISSN | 2666-979X |
| Abstract | Large-scale single-cell atlases have revealed many aging- and disease-associated cell types, yet these populations are often underrepresented in heterogeneous tissues, limiting detailed molecular analyses. To address this, we developed EnrichSci-a scalable, microfluidics-free platform that combines hybridization chain reaction RNA fluorescence in situ hybridization (FISH) with combinatorial indexing to profile single-nucleus transcriptomes of target cell types with full gene-body coverage. Applied to oligodendrocytes in the aging mouse brain, EnrichSci uncovered aging-associated molecular dynamics across distinct oligodendrocyte subtypes, revealing both shared and subtype-specific gene expression changes. Additionally, we identified aging-associated exon-level signatures missed by conventional gene-level analyses, highlighting post-transcriptional regulation as a critical dimension of cell-state dynamics in aging. By coupling transcript-guided enrichment with a scalable sequencing workflow, EnrichSci provides a versatile approach to decode dynamic regulatory landscapes in diverse cell types from complex tissues. |
| DOI | 10.1016/j.xgen.2025.101101 |
| PubMed ID | 41386229 |