High resolution single-cell transcriptomics towards precision profiling across multi-omics and spatial dimensions

Abstract

Cellular heterogeneity poses major researchers challenges. Tag-based single-cell RNA sequencing (scRNA-seq) methods enables cell-type classification and population diversity in biological systems but lacks resolution for splicing regulation, allele expression, isoform diversity, transcriptional mutation, and the identification of comprehensive RNA types. High-resolution full-length scRNA-seq offers significant advantages in achieving molecular resolution for transcript-level quantification, structural variations detection, and the identification of comprehensive RNA types. It has been widely applied in refines cell fate determination models. Additionally, integrating full-length scRNA-seq technology with multi-omics and spatially resolved sequencing will decipher cellular interactions and their cross-modality molecular mechanisms more precisely. This review focuses on the latest iterative technology of high resolution scRNA-seq spanning poly(A+) mRNA to total RNA full-length capture systems, precision profiling methods across multi-omics and spatial dimensions, and their applications in tumor biology, reproductive medicine, immunology, and developmental biology. Finally, current challenges and prospectives are discussed.