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@ARTICLE{Scherer:301579,
author = {M. Scherer$^*$ and I. Singh and M. M. Braun and C. Szu-Tu
and P. Sanchez Sanchez and D. Lindenhofer and N. A. Jakobsen
and V. Körber and M. Kardorff and L. Nitsch and P. Kautz
and J. Rühle and A. Bianchi and L. Cozzuto and R. Frömel
and S. Beneyto-Calabuig and C. Lareau and A. T. Satpathy and
R. Beekman and L. M. Steinmetz and S. Raffel and L. S.
Ludwig and P. Vyas and A. Rodriguez-Fraticelli and L.
Velten},
title = {{C}lonal tracing with somatic epimutations reveals dynamics
of blood ageing.},
journal = {Nature},
volume = {643},
number = {8071},
issn = {0028-0836},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2025-01087},
pages = {478-487},
year = {2025},
note = {#EA:B370# / 2025 Jul;643(8071):478-487},
abstract = {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.},
cin = {B370},
ddc = {500},
cid = {I:(DE-He78)B370-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40399669},
doi = {10.1038/s41586-025-09041-8},
url = {https://inrepo02.dkfz.de/record/301579},
}