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Mincarelli, Laura, Uzun, Vladimir, Wright, David, Scoones, Anita, Rushworth, Stuart A., Haerty, Wilfried 
ORCID: https://orcid.org/0000-0003-0111-191X and Macaulay, Iain C.
(2023)
Single-cell gene and isoform expression analysis reveals signatures of ageing in haematopoietic stem and progenitor cells.
Communications Biology, 6.
ISSN 2399-3642
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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.
| Item Type: | Article |
|---|---|
| Additional Information: | Data availability: Sequencing data can be accessed on the NCBI-GEO archive, accession number GSE166709. Source data for the graphs and charts are given in Supplementary Data 4, and any remaining information can be obtained from the corresponding authors upon reasonable request. Funding Information: I.C.M. is supported by a BBSRC New Investigator Grant [BB/P022073/1] and the BBSRC National Capability in Genomics and Single Cell Analysis at Earlham Institute [BB/CCG1720/1]. W.H., L.M. and D.W. are supported by the BBSRC Core Strategic Programme Grant [BB/P016774/1], and W.H. by a UK Medical Research Council [MR/P026028/1] award. S.R. is funded by the Rosetrees Trust, The Big C and the Medical Research Council [MR/T02934X/1]. Next-generation sequencing was delivered via the BBSRC National Capability in Genomics and Single Cell Analysis [BB/CCG1720/1] at Earlham Institute. |
| Uncontrolled Keywords: | medicine (miscellaneous),biochemistry, genetics and molecular biology(all),agricultural and biological sciences(all) ,/dk/atira/pure/subjectarea/asjc/2700/2701 |
| Faculty \ School: | Faculty of Science > School of Pharmacy Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Science > Research Groups > Patient Care Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies |
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| Depositing User: | LivePure Connector |
| Date Deposited: | 21 Mar 2024 17:30 |
| Last Modified: | 21 Mar 2024 17:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/94739 |
| DOI: | 10.1038/s42003-023-04936-6 |
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