TY  - JOUR
AU  - Lalioti, Maria-Eleni
AU  - Romero-Mulero, Mari Carmen
AU  - Karabacz, Noémie
AU  - Mess, Julian
AU  - Demollin, Helen
AU  - Rettkowski, Jasmin
AU  - Schuldes, Konrad
AU  - Mitterer, Michael
AU  - Wadle, Carolin
AU  - Shoumariyeh, Khalid
AU  - Egg, Mirijam
AU  - Alfonso-Gonzalez, Carlos
AU  - Jäcklein, Karin
AU  - Schönberger, Katharina
AU  - Karantzelis, Nikolaos
AU  - Reisig, Gregor
AU  - Aktories, Philipp
AU  - Mayer, Isabella M
AU  - Tsoukala, Ioanna
AU  - Schäffer, Alexander
AU  - Tirado-Gonzalez, Irene
AU  - Dugourd, Aurélien
AU  - Braun, Lukas M
AU  - Silva-Rego, Beatriz
AU  - Jones, Michael-Jason
AU  - Kierdorf, Katrin
AU  - Saez-Rodriguez, Julio
AU  - Reising, Kilian
AU  - Walter, Sebastian Gottfried
AU  - Medyouf, Hind
AU  - Hilgers, Valérie
AU  - Ghiaur, Gabriel
AU  - Zeiser, Robert
AU  - Karpova, Darja
AU  - Renders, Simon
AU  - Gravius, Sascha
AU  - Buescher, Joerg
AU  - Cabezas-Wallscheid, Nina
TI  - Differentiation, ageing and leukaemia alter the metabolic profile of human bone marrow haematopoietic stem and progenitor cells.
JO  - Nature cell biology
VL  - 27
IS  - 8
SN  - 1465-7392
CY  - New York, NY
PB  - Nature America
M1  - DKFZ-2025-01396
SP  - 1367-1380
PY  - 2025
N1  - 2025 Aug;27(8):1367-1380
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:40664811
DO  - DOI:10.1038/s41556-025-01709-7
UR  - https://inrepo02.dkfz.de/record/302856
ER  -