TY  - JOUR
AU  - Scherer, Michael
AU  - Singh, Indranil
AU  - Braun, Martina Maria
AU  - Szu-Tu, Chelsea
AU  - Sanchez Sanchez, Pedro
AU  - Lindenhofer, Dominik
AU  - Jakobsen, Niels Asger
AU  - Körber, Verena
AU  - Kardorff, Michael
AU  - Nitsch, Lena
AU  - Kautz, Pauline
AU  - Rühle, Julia
AU  - Bianchi, Agostina
AU  - Cozzuto, Luca
AU  - Frömel, Robert
AU  - Beneyto-Calabuig, Sergi
AU  - Lareau, Caleb
AU  - Satpathy, Ansuman T
AU  - Beekman, Renée
AU  - Steinmetz, Lars M
AU  - Raffel, Simon
AU  - Ludwig, Leif S
AU  - Vyas, Paresh
AU  - Rodriguez-Fraticelli, Alejo
AU  - Velten, Lars
TI  - Clonal tracing with somatic epimutations reveals dynamics of blood ageing.
JO  - Nature
VL  - 643
IS  - 8071
SN  - 0028-0836
CY  - London [u.a.]
PB  - Nature Publ. Group
M1  - DKFZ-2025-01087
SP  - 478-487
PY  - 2025
N1  - #EA:B370# / 2025 Jul;643(8071):478-487
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:40399669
DO  - DOI:10.1038/s41586-025-09041-8
UR  - https://inrepo02.dkfz.de/record/301579
ER  -