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  3. Differentiation, ageing and leukaemia alter the metabolic profile of human bone marrow haematopoietic stem and progenitor cells

Differentiation, ageing and leukaemia alter the metabolic profile of human bone marrow haematopoietic stem and progenitor cells

  • Nat Cell Biol. 2025 Aug;27(8):1367-1380. doi: 10.1038/s41556-025-01709-7.
Maria-Eleni Lalioti # 1 2,  Mari Carmen Romero-Mulero # 1 2 3,  Noémie Karabacz 1 3 4,  Julian Mess 1 3 5,  Helen Demollin 1 3,  Jasmin Rettkowski 1 2 3,  Konrad Schuldes 1,  Michael Mitterer 1,  Carolin Wadle 1 2,  Khalid Shoumariyeh 6 7,  Mirijam Egg 1 3 4,  Carlos Alfonso-Gonzalez 1,  Karin Jäcklein 1,  Katharina Schönberger 1 8,  Nikolaos Karantzelis 6,  Gregor Reisig 9,  Philipp Aktories 3 10,  Isabella M Mayer 2,  Ioanna Tsoukala 11,  Alexander Schäffer 11,  Irene Tirado-Gonzalez 11,  Aurélien Dugourd 12,  Lukas M Braun 6,  Beatriz Silva-Rego 1,  Michael-Jason Jones 1 3,  Katrin Kierdorf 5 10,  Julio Saez-Rodriguez 12,  Kilian Reising 13,  Sebastian Gottfried Walter 14,  Hind Medyouf 11 15 16,  Valérie Hilgers 1,  Gabriel Ghiaur 17,  Robert Zeiser 6,  Darja Karpova 18,  Simon Renders 19,  Sascha Gravius 9,  Joerg Buescher 20,  Nina Cabezas-Wallscheid 21 22 23
Affiliations

Affiliations

  • 1 Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
  • 2 Laboratory of Stem Cell Biology and Ageing, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH Zürich), Zurich, Switzerland.
  • 3 University of Freiburg, Faculty of Biology, Freiburg, Germany.
  • 4 International Max Planck Research School of Immunobiology, Epigenetics and Metabolism, Freiburg, Germany.
  • 5 Centre for Integrative Biological Signalling Studies, Freiburg, Germany.
  • 6 Department of Medicine I - Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • 7 German Cancer Consortium (DKTK), Partner Site Freiburg, a Partnership Between DKFZ and Medical Center, University of Freiburg, Freiburg, Germany.
  • 8 Laboratory of Exercise and Health, Department Health Sciences and Technology, Swiss Federal Institute of Technology (ETH Zürich), Zurich, Switzerland.
  • 9 Department of Orthopaedic and Trauma Surgery, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
  • 10 Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • 11 Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany.
  • 12 Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg University, Heidelberg, Germany.
  • 13 Department of Orthopedic Surgery and Traumatology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
  • 14 Department of Orthopedics, Traumatology and Reconstructive Surgery, University Hospital Cologne, Cologne, Germany.
  • 15 Frankfurt Cancer Institute, Frankfurt am Main, Germany.
  • 16 Department of Hematology Oncology, University Hospital Aachen, Aachen, Germany.
  • 17 Division of Hematological Malignancies, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University Hospital, Baltimore, MD, USA.
  • 18 Institute for Transfusion Medicine and Immunohematology, Goethe University Hospital Medical School, German Red Cross Blood Donor Service, Frankfurt am Main, Germany.
  • 19 Department of Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.
  • 20 Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany. buescher@ie-freiburg.mpg.de.
  • 21 Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany. nina.cabezas@hest.ethz.ch.
  • 22 Laboratory of Stem Cell Biology and Ageing, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH Zürich), Zurich, Switzerland. nina.cabezas@hest.ethz.ch.
  • 23 Centre for Integrative Biological Signalling Studies, Freiburg, Germany. nina.cabezas@hest.ethz.ch.
  • # Contributed equally.
PMID: 40664811 DOI: 10.1038/s41556-025-01709-7
Abstract

Metabolic cues are crucial for regulating haematopoietic stem and progenitor cells (HSPCs). However, the metabolic profile of human HSPCs remains poorly understood due to the limited number of cells and the scarcity of bone marrow samples. Here we present the integrated metabolome, lipidome and transcriptome of human adult HSPCs (lineage-, CD34+, CD38-) upon differentiation, ageing and acute myeloid leukaemia. The combination of low-input targeted metabolomics with our newly optimized low-input untargeted lipidomics workflow allows us to detect up to 193 metabolites and lipids from a starting material of 3,000 and 5,000 HSPCs, respectively. Among Other findings, we observe elevated levels of the essential nutrient choline in HSPCs compared with downstream progenitors, which decline upon ageing and further decrease in acute myeloid leukaemia. Functionally, we show that choline supplementation fuels lipid production in HSPCs and enhances stemness. Overall, our study provides a comprehensive resource identifying metabolic changes that can be utilized to promote and enhance human stem cell function.

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