Differentiation, ageing and leukaemia alter the metabolic profile of human bone marrow haematopoietic stem and progenitor cells
Maria‐Eleni Lalioti, Mari Carmen Romero-Mulero, Noémie Karabacz, Julian Mess, Helen Demollin, Jasmin Rettkowski, Konrad Schuldes, Michael Mitterer, Carolin Wadle, Khalid Shoumariyeh, Mirijam Egg, Carlos Alfonso-Gonzalez, Karin Jäcklein, Katharina Schönberger, Nikolaos Karantzelis, Gregor Reisig, Philipp Aktories, Isabella Maria Mayer, Ioanna Tsoukala, Alexander Schäffer, Irene Tirado‐González, Aurélien Dugourd, Lukas M. Braun, Beatriz Silva-Rego, Marion Jones, Katrin Kierdorf, Julio Sáez-Rodríguez, Kilian Reising, Sebastian G. Walter, Hind Medyouf, Valérie Hilgers, Gabriel Ghiaur, Robert Zeiser, Darja Karpova, Simon Renders, Sascha Gravius, Joerg M. Buescher, Nina Cabezas‐Wallscheid
Abstract
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.