Clonal tracing with somatic epimutations reveals dynamics of blood ageing
Current approaches used to track stem cell clones through differentiation require genetic engineering1,2 or rely on sparse somatic DNA variants3,4, which limits their wide application. Here we discover that DNA methylation of a subset of CpG sites reflects cellular differentiation, whereas another s...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
10 July 2025
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| In: |
Nature
Year: 2025, Jahrgang: 643, Heft: 8071, Pages: 478487 |
| ISSN: | 14764687 |
| DOI: | 10.1038/s41586-025-09041-8 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41586-025-09041-8 Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41586-025-09041-8 
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| Verfasserangaben: | Michael Scherer, Indranil Singh, Martina Maria Braun, Chelsea Szu-Tu, Pedro Sanchez Sanchez, Dominik Lindenhofer, Niels Asger Jakobsen, Verena Körber, Michael Kardorff, Lena Nitsch, Pauline Kautz, Julia Rühle, Agostina Bianchi, Luca Cozzuto, Robert Frömel, Sergi Beneyto-Calabuig, Caleb Lareau, Ansuman T. Satpathy, Renée Beekman, Lars M. Steinmetz, Simon Raffel, Leif S. Ludwig, Paresh Vyas, Alejo Rodriguez-Fraticelli & Lars Velten |
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| 245 | 1 | 0 | |a Clonal tracing with somatic epimutations reveals dynamics of blood ageing |c Michael Scherer, Indranil Singh, Martina Maria Braun, Chelsea Szu-Tu, Pedro Sanchez Sanchez, Dominik Lindenhofer, Niels Asger Jakobsen, Verena Körber, Michael Kardorff, Lena Nitsch, Pauline Kautz, Julia Rühle, Agostina Bianchi, Luca Cozzuto, Robert Frömel, Sergi Beneyto-Calabuig, Caleb Lareau, Ansuman T. Satpathy, Renée Beekman, Lars M. Steinmetz, Simon Raffel, Leif S. Ludwig, Paresh Vyas, Alejo Rodriguez-Fraticelli & Lars Velten |
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| 520 | |a Current approaches used to track stem cell clones through differentiation require genetic engineering1,2 or rely on sparse somatic DNA variants3,4, which limits their wide application. Here we discover that DNA methylation of a subset of CpG sites reflects cellular differentiation, whereas another subset undergoes stochastic epimutations and can serve as digital barcodes of clonal identity. We demonstrate that targeted single-cell profiling of DNA methylation5 at single-CpG resolution can accurately extract both layers of information. To that end, we develop EPI-Clone, a method for transgene-free lineage tracing at scale. Applied to mouse and human haematopoiesis, we capture hundreds of clonal differentiation trajectories across tens of individuals and 230,358 single cells. In mouse ageing, we demonstrate that myeloid bias and low output of old haematopoietic stem cells6 are restricted to a small number of expanded clones, whereas many functionally young-like clones persist in old age. In human ageing, clones with and without known driver mutations of clonal haematopoieis7 are part of a spectrum of age-related clonal expansions that display similar lineage biases. EPI-Clone enables accurate and transgene-free single-cell lineage tracing on hematopoietic cell state landscapes at scale. | ||
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