A comprehensive transcriptome signature of murine hematopoietic stem cell aging
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Abstract
We surveyed 16 published and unpublished data sets to determine whether a consistent pattern of transcriptional deregulation in aging murine hematopoietic stem cells (HSC) exists. Despite substantial heterogeneity between individual studies, we uncovered a core and robust HSC aging signature. We detected increased transcriptional activation in aged HSCs, further confirmed by chromatin accessibility analysis. Unexpectedly, using 2 independent computational approaches, we established that deregulated aging genes consist largely of membrane-associated transcripts, including many cell surface molecules previously not associated with HSC biology. We show that Selp (P-selectin), the most consistent deregulated gene, is not merely a marker for aged HSCs but is associated with HSC functional decline. Additionally, single-cell transcriptomics analysis revealed increased heterogeneity of the aged HSC pool. We identify the presence of transcriptionally “young-like” HSCs in aged bone marrow. We share our results as an online resource and demonstrate its utility by confirming that exposure to sympathomimetics or deletion of Dnmt3a/b molecularly resembles HSC rejuvenation or aging, respectively.
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Upregulation of cell adhesion markers in HSCs may be a direct indicator of their inflammatory state and may correlate with the bias towards myeloid cell production.
“Upregulation of cell adhesion markers in HSCs may be a direct indicator of their inflammatory state and may correlate with the bias towards myeloid cell production68.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [68]
A comprehensive analysis of murine HSC ageing has found increased chromatin accessibility and an overall increase in transcription.
“A comprehensive analysis of murine HSC ageing has found increased chromatin accessibility and an overall increase in transcription68.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [68]
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Ageing and rejuvenation of tissue stem cells and their niches
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- Authors
- Flohr Svendsen, A., Yang, D., Kim, K., Lazare, S., Skinder, N., Zwart, E., Mura-Meszaros, A., Ausema, A., von Eyss, B., de Haan, G., & Bystrykh, L.
- Affiliations
- European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and
- University Medical Center Groningen (NL)
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Transcriptional Control of Tissue Homeostasis Laboratory, Leibniz Institute on Aging, Fritz Lipmann Institute e.V., Jena, Germany
- Corresponding author
- Bystrykh, Leonid
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2021-04-19
- Volume
- 138
- Issue
- 6
- Pages
- 439-451
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W3155253210
- Cited by
- 138
- References
- 56
- Citations by year
- 2026: 20 · 2025: 35 · 2024: 31 · 2023: 27 · 2022: 20 · 2021: 5
- FWCI
- 8.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- SSRN Electronic Journal (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Landsteiner Foundation for Blood Transfusion Research
- Australian Government
- European Commission (316964, EU-FP7, 813091, EU FP7 Marie Curie, HORIZON2020)
- Deutsche Forschungsgemeinschaft (EY 120/1-1)
- Universitair Medisch Centrum Groningen
- Deutsche Krebshilfe (70113138)
- Leibniz-Gemeinschaft
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- hematopoietic stem cell aging, transcriptome signature, transcriptional dysregulation, chromatin accessibility, cell surface molecules, P-selectin, HSC heterogeneity, sympathomimetic drugs, bone marrow
- MeSH terms
- Animals, Hematopoietic Stem Cells, Mice, Transgenic, Cellular Senescence, Gene Expression Profiling, Mice, Transcriptome
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