{"doi":"10.1101/2024.04.01.587514","title":"Somatic epimutations enable single-cell lineage tracing in native hematopoiesis across the murine and human lifespan","abstract":"<jats:title>Summary</jats:title>\n                <jats:p>Current approaches to lineage tracing of stem cell clones require genetic engineering or rely on sparse somatic DNA variants, which are difficult to capture at single-cell resolution. Here, we show that targeted single-cell measurements of DNA methylation at single-CpG resolution deliver joint information about cellular differentiation state and clonal identities. We develop EPI-clone, a droplet-based method for transgene-free lineage tracing, and apply it to study hematopoiesis, capturing hundreds of clonal trajectories across almost 100,000 single-cells. Using ground-truth genetic barcodes, we demonstrate that EPI-clone accurately identifies clonal lineages throughout hematopoietic differentiation. Applied to unperturbed hematopoiesis, we describe an overall decline of clonal complexity during murine ageing and the expansion of rare low-output stem cell clones. In aged human donors, we identified expanded hematopoietic clones with and without genetic lesions, and various degrees of clonal complexity. Taken together, EPI-clone enables accurate and transgene-free single-cell lineage tracing at scale.</jats:p>","journal":null,"year":null,"id":627204,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1622917,"name":"Indranil Singh","orcid":"0000-0002-2143-986X","position":1,"is_corresponding":false},{"id":176749,"name":"Martina Braun","orcid":null,"position":2,"is_corresponding":false},{"id":1622918,"name":"Chelsea Szu-Tu","orcid":"0000-0001-9990-4883","position":3,"is_corresponding":false},{"id":1410880,"name":"Michael Kardorff","orcid":"0009-0008-9720-6166","position":4,"is_corresponding":false},{"id":1622919,"name":"Julia Rühle","orcid":"0000-0002-1479-3633","position":5,"is_corresponding":false},{"id":1326033,"name":"Robert Frömel","orcid":"0000-0002-0438-8677","position":6,"is_corresponding":false},{"id":990951,"name":"Sergi Beneyto‐Calabuig","orcid":"0000-0003-3773-8239","position":7,"is_corresponding":false},{"id":852394,"name":"Simon Raffel","orcid":"0000-0003-4671-1097","position":8,"is_corresponding":false},{"id":108924,"name":"Alejo Rodriguez-Fraticelli","orcid":"0000-0002-4017-8714","position":9,"is_corresponding":false},{"id":870977,"name":"Lars Velten","orcid":"0000-0002-1233-5874","position":10,"is_corresponding":false},{"id":1622916,"name":"Michael Scherer","orcid":"0000-0001-7990-6179","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Somatic epimutations enable single-cell lineage tracing in native hematopoiesis across the murine and human lifespan","abstract":"<jats:title>Summary</jats:title>\n                <jats:p>Current approaches to lineage tracing of stem cell clones require genetic engineering or rely on sparse somatic DNA variants, which are difficult to capture at single-cell resolution. Here, we show that targeted single-cell measurements of DNA methylation at single-CpG resolution deliver joint information about cellular differentiation state and clonal identities. We develop EPI-clone, a droplet-based method for transgene-free lineage tracing, and apply it to study hematopoiesis, capturing hundreds of clonal trajectories across almost 100,000 single-cells. Using ground-truth genetic barcodes, we demonstrate that EPI-clone accurately identifies clonal lineages throughout hematopoietic differentiation. Applied to unperturbed hematopoiesis, we describe an overall decline of clonal complexity during murine ageing and the expansion of rare low-output stem cell clones. In aged human donors, we identified expanded hematopoietic clones with and without genetic lesions, and various degrees of clonal complexity. Taken together, EPI-clone enables accurate and transgene-free single-cell lineage tracing at scale.</jats:p>","is_dataset_classified":null,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38617287","pmcid":null,"openalex_id":"https://openalex.org/W4393444698","authors":[],"funders":[{"funder_name":"European Commission","grant_id":"101042992","title":"Origins and Consequences of Hematopoietic Stem Cell Memories"},{"funder_name":"National Institutes of Health","grant_id":"1K99HL146983-01","title":"mechanisms of in situ functional stem cell heterogeneity in native and transplantation hematopoiesis"},{"funder_name":"European Commission","grant_id":"945352","title":"IRB DoctoRal fEllowship ProgrAMme: attracting international talent (IRB_DREAM)"},{"funder_name":"NHLBI NIH HHS","grant_id":"K99 HL146983","title":null}],"total_grants":4,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2024,"count":6},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"green","license":"cc-by-nc","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2024/04/01/2024.04.01.587514.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2024/04/01/2024.04.01.587514.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2024.04.01.587514","host_type":"publisher"},{"url":"https://doi.org/10.1101/2024.04.01.587514","host_type":"repository"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38617287","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11014487","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11014487/pdf/nihpp-2024.04.01.587514v1.pdf","host_type":"repository"},{"url":"http://dx.doi.org/10.1101/2024.04.01.587514","host_type":""}],"fields_of_study":["Single-cell and spatial transcriptomics","Cancer Genomics and Diagnostics","Epigenetics and DNA Methylation","0301 basic medicine","03 medical and health sciences"],"mesh_terms":[],"keywords":["Biology","Somatic cell","clone (Java method)","Lineage (genetic)","Haematopoiesis","Cell lineage","Stem cell","Single-cell analysis","Transgene","Genetics","Computational biology","Cell biology","Cell","Gene","Cellular differentiation","Article"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Responsible consumption and production"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T16:41:24.793335Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}