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000301579 1001_ $$0P:(DE-He78)684b935434c8fe314d2cf6bd023d384b$$aScherer, Michael$$b0$$eFirst author$$udkfz
000301579 245__ $$aClonal tracing with somatic epimutations reveals dynamics of blood ageing.
000301579 260__ $$aLondon [u.a.]$$bNature Publ. Group$$c2025
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000301579 500__ $$a#EA:B370# / 2025 Jul;643(8071):478-487
000301579 520__ $$aCurrent approaches used to track stem cell clones through differentiation require genetic engineering1,2 or rely on sparse somatic DNA variants3,4, which limits their wide application. Here we discover that DNA methylation of a subset of CpG sites reflects cellular differentiation, whereas another subset undergoes stochastic epimutations and can serve as digital barcodes of clonal identity. We demonstrate that targeted single-cell profiling of DNA methylation5 at single-CpG resolution can accurately extract both layers of information. To that end, we develop EPI-Clone, a method for transgene-free lineage tracing at scale. Applied to mouse and human haematopoiesis, we capture hundreds of clonal differentiation trajectories across tens of individuals and 230,358 single cells. In mouse ageing, we demonstrate that myeloid bias and low output of old haematopoietic stem cells6 are restricted to a small number of expanded clones, whereas many functionally young-like clones persist in old age. In human ageing, clones with and without known driver mutations of clonal haematopoieis7 are part of a spectrum of age-related clonal expansions that display similar lineage biases. EPI-Clone enables accurate and transgene-free single-cell lineage tracing on hematopoietic cell state landscapes at scale.
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000301579 7001_ $$00000-0002-2143-986X$$aSingh, Indranil$$b1
000301579 7001_ $$aBraun, Martina Maria$$b2
000301579 7001_ $$aSzu-Tu, Chelsea$$b3
000301579 7001_ $$00000-0002-4846-1813$$aSanchez Sanchez, Pedro$$b4
000301579 7001_ $$00000-0001-8838-7163$$aLindenhofer, Dominik$$b5
000301579 7001_ $$00000-0002-5776-5085$$aJakobsen, Niels Asger$$b6
000301579 7001_ $$aKörber, Verena$$b7
000301579 7001_ $$00009-0008-9720-6166$$aKardorff, Michael$$b8
000301579 7001_ $$aNitsch, Lena$$b9
000301579 7001_ $$00000-0002-9658-1676$$aKautz, Pauline$$b10
000301579 7001_ $$aRühle, Julia$$b11
000301579 7001_ $$aBianchi, Agostina$$b12
000301579 7001_ $$aCozzuto, Luca$$b13
000301579 7001_ $$00000-0002-0438-8677$$aFrömel, Robert$$b14
000301579 7001_ $$00000-0003-3773-8239$$aBeneyto-Calabuig, Sergi$$b15
000301579 7001_ $$00000-0003-4179-4807$$aLareau, Caleb$$b16
000301579 7001_ $$00000-0002-5167-537X$$aSatpathy, Ansuman T$$b17
000301579 7001_ $$00000-0001-7081-7874$$aBeekman, Renée$$b18
000301579 7001_ $$aSteinmetz, Lars M$$b19
000301579 7001_ $$aRaffel, Simon$$b20
000301579 7001_ $$00000-0002-2916-2164$$aLudwig, Leif S$$b21
000301579 7001_ $$00000-0003-3931-0914$$aVyas, Paresh$$b22
000301579 7001_ $$00000-0002-4017-8714$$aRodriguez-Fraticelli, Alejo$$b23
000301579 7001_ $$00000-0002-1233-5874$$aVelten, Lars$$b24
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