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bioRxiv · 10.1101/2025.05.02.651937

EnrichSci: Transcript-guided Targeted Cell Enrichment for Scalable Single-Cell RNA Sequencing

Liao, A.·Zhang, Z.·Sziraki, A.·Abdulraouf, A.·Xu, Z.·Lu, Z.·Zhou, W.·Cao, J.
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Abstract

Large-scale single-cell atlas efforts have revealed many aging-or disease-associated cell types, yet these populations are often underrepresented in heterogeneous tissues, limiting detailed molecular and dynamic analyses. To address this, we developed EnrichSci--a highly scalable, microfluidics-free platform that combines Hybridization Chain Reaction RNA FISH with combinatorial indexing to profile single -nucleus transcriptomes of targeted cell types with full gene-body coverage. When applied to profile 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 that are 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.

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Liao, A., Zhang, Z., Sziraki, A., Abdulraouf, A., Xu, Z., Lu, Z., Zhou, W., Cao, J.. 2025-05-08. EnrichSci: Transcript-guided Targeted Cell Enrichment for Scalable Single-Cell RNA Sequencing. https://doi.org/10.1101/2025.05.02.651937

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