Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate
Open accessAbstract
Ageing associates with significant alterations in somatic/adult stem cells and therapies to counteract these might have profound benefits for health. In the blood, haematopoietic stem cell (HSC) ageing is linked to several functional shortcomings. However, besides the recent realization that individual HSCs might be preset differentially already from young age, HSCs might also age asynchronously. Evaluating the prospects for HSC rejuvenation therefore ultimately requires approaching those HSCs that are functionally affected by age. Here we combine genetic barcoding of aged murine HSCs with the generation of induced pluripotent stem (iPS) cells. This allows us to specifically focus on aged HSCs presenting with a pronounced lineage skewing, a hallmark of HSC ageing. Functional and molecular evaluations reveal haematopoiesis from these iPS clones to be indistinguishable from that associating with young mice. Our data thereby provide direct support to the notion that several key functional attributes of HSC ageing can be reversed.
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Some aging phenotypes can be reversed by reprogramming aged HSCs to pluripotency and deriving definitive hematopoiesis from the resulting iPSCs.
“In fact, reversal of some aging phenotypes has been achieved by reprogramming old HSCs to pluripotency and subsequently generating definitive hematopoiesis from these induced pluripotent stem cells.107”
From Aging of hematopoietic stem cells (2018) · cites this paper as [107]
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References 29 · Cited by 59
- Authors
- Wahlestedt, M., Erlandsson, E., Kristiansen, T., Lu, R., Brakebusch, C., Weissman, I. L., Yuan, J., Martin-Gonzalez, J., & Bryder, D.
- Affiliations
- Lund University (SE)
- University of Southern California (US)
- University of Copenhagen (DK)
- Institute for Stem Cell Biology and Regenerative Medicine (US)
- Corresponding author
- Bryder, David
- Venue
- Nature Communications
- Published
- 2017-02-22
- Volume
- 8
- Issue
- 1
- Pages
- 14533-14533
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5322498
- OpenAlex
- W2591403727
- Cited by
- 59
- References
- 29
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 10 · 2020: 8 · 2019: 5 · 2018: 2 · 2017: 4
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Cancerfonden (615068)
- Knut och Alice Wallenbergs Stiftelse
- Medical Research Council
- FP7 Ideas: European Research Council (615068)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- induced pluripotent stem cells, stem cell rejuvenation, clonal analysis, DNA barcoding, hematopoiesis
- MeSH terms
- Aging, Animals, Clone Cells, Hematopoietic Stem Cells, Mice, Inbred C57BL, T-Lymphocytes, Cellular Senescence, Gene Expression Regulation, Developmental, Cell Lineage, Induced Pluripotent Stem Cells, Cellular Reprogramming
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