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- Title
Single-cell gene and isoform expression analysis reveals signatures of ageing in haematopoietic stem and progenitor cells.
- Authors
Mincarelli, Laura; Uzun, Vladimir; Wright, David; Scoones, Anita; Rushworth, Stuart A.; Haerty, Wilfried; Macaulay, Iain C.
- Abstract
Single-cell approaches have revealed that the haematopoietic hierarchy is a continuum of differentiation, from stem cell to committed progenitor, marked by changes in gene expression. However, many of these approaches neglect isoform-level information and thus do not capture the extent of alternative splicing within the system. Here, we present an integrated short- and long-read single-cell RNA-seq analysis of haematopoietic stem and progenitor cells. We demonstrate that over half of genes detected in standard short-read single-cell analyses are expressed as multiple, often functionally distinct, isoforms, including many transcription factors and key cytokine receptors. We observe global and HSC-specific changes in gene expression with ageing but limited impact of ageing on isoform usage. Integrating single-cell and cell-type-specific isoform landscape in haematopoiesis thus provides a new reference for comprehensive molecular profiling of heterogeneous tissues, as well as novel insights into transcriptional complexity, cell-type-specific splicing events and consequences of ageing. Single-cell transcriptomics using long-read sequencing achieves both gene and isoform expression in haematopoietic stem and progenitor cells, providing novel insights into the understanding of alternative splicing in cellular differentiation.
- Subjects
HEMATOPOIETIC stem cells; GENE expression; ALTERNATIVE RNA splicing; CYTOKINE receptors; RNA splicing; STEM cells; TRANSCRIPTION factors
- Publication
Communications Biology, 2023, Vol 6, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-023-04936-6