Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics

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  • dc.contributor.author Velten, Lars
  • dc.contributor.author Story, Benjamin A.
  • dc.contributor.author Hernández-Malmierca, Pablo
  • dc.contributor.author Raffel, Simon
  • dc.contributor.author Leonce, Daniel R.
  • dc.contributor.author Milbank, Jennifer
  • dc.contributor.author Paulsen, Malte
  • dc.contributor.author Demir, Aykut
  • dc.contributor.author Szu-Tu, Chelsea
  • dc.contributor.author Frömel, Robert
  • dc.contributor.author Lutz, Christoph
  • dc.contributor.author Novak, Daniel
  • dc.contributor.author Jann, Johann-Christoph
  • dc.contributor.author Pabst, Caroline
  • dc.contributor.author Boch, Tobias
  • dc.contributor.author Hofmann, Wolf-Karsten
  • dc.contributor.author Müller-Tidow, Carsten
  • dc.contributor.author Trumpp, Andreas
  • dc.contributor.author Haas, Simon
  • dc.contributor.author Steinmetz, Lars M.
  • dc.date.accessioned 2021-03-23T11:10:38Z
  • dc.date.available 2021-03-23T11:10:38Z
  • dc.date.issued 2021
  • dc.description.abstract Cancer stem cells drive disease progression and relapse in many types of cancer. Despite this, a thorough characterization of these cells remains elusive and with it the ability to eradicate cancer at its source. In acute myeloid leukemia (AML), leukemic stem cells (LSCs) underlie mortality but are difficult to isolate due to their low abundance and high similarity to healthy hematopoietic stem cells (HSCs). Here, we demonstrate that LSCs, HSCs, and pre-leukemic stem cells can be identified and molecularly profiled by combining single-cell transcriptomics with lineage tracing using both nuclear and mitochondrial somatic variants. While mutational status discriminates between healthy and cancerous cells, gene expression distinguishes stem cells and progenitor cell populations. Our approach enables the identification of LSC-specific gene expression programs and the characterization of differentiation blocks induced by leukemic mutations. Taken together, we demonstrate the power of single-cell multi-omic approaches in characterizing cancer stem cells.
  • dc.description.sponsorship This project was financially supported by the Deutsche José Carreras Leukämie Stiftung grant DJCLS 20R/2017 (to L.V., S.H., L.M.S., and A.T.), the Emerson foundation grant 643577 (to L.V. and L.M.S.) and the German Bundesministerium für Bildung und Forschung (BMBF) through the Juniorverbund in der Systemmedizin “LeukoSyStem” (FKZ 01ZX1911D to L.V., S.H., and S.R). Contributions by S.R. were further supported by Emmy Noether Fellowship RA 3166/1-1 (DFG). Contributions by C.P. were supported by a Max-Eder Grant (German Cancer Aid 70111531). Contributions by D.N., J.C.J., W.K.H., and T.B. were supported by the Gutermuth Foundation, the H.W. & J. Hector fund, Baden-Württemberg, and the Dr. Rolf M. Schwiete Fund, Mannheim. D.N. is an endowed professor of the Deutsche José Carreras Leukämie Stiftung (DJCLS H 03/01)
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Velten L, Story BA, Hernández-Malmierca P, Raffel S, Leonce DR, Milbank J et al. Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics. Nat Commun. 2021 Mar 1; 12(1): 1366. DOI: 10.1038/s41467-021-21650-1
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-021-21650-1
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/46904
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nature Communications. 2021 Mar 1;12(1):1366
  • dc.rights © Lars Velten et al 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Genètica
  • dc.subject.other Leucèmia
  • dc.subject.other Cèl·lules mare
  • dc.title Identification of leukemic and pre-leukemic stem cells by clonal tracking from single-cell transcriptomics
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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