德国马克斯·普朗克免疫生物学和表观遗传学研究所Nina Cabezas-Wallscheid小组的研究发现，分化、衰老和白血病改变了人骨髓造血干细胞和祖细胞的代谢谱。这一研究成果发表在2025年7月15日出版的国际学术期刊《自然—细胞生物学》上。

在这里，课题组人员展示了分化、衰老和急性髓系白血病后人类成人HSPCs（谱系）的综合代谢组、脂质组和转录组（谱系^-、cd34⁺ 、cd38^-)。低输入靶向代谢组学与他们新优化的低输入非靶向脂质组学工作流程相结合，使他们能够分别从3000和5000个HSPCs的起始材料中检测多达193种代谢物和脂质。在其他发现中，该课题组观察到与下游祖细胞相比，HSPCs中必需营养素胆碱水平升高，胆碱随年龄增长而下降，急性髓性白血病进一步下降。在功能上，该研究组发现补充胆碱可以促进HSPCs的脂质生成并增强其干性。总的来说，他们的研究提供了一个全面的抵抗，确定可用于促进和增强人类干细胞功能的代谢变化。

研究人员表示，代谢线索对调节造血干细胞和祖细胞（HSPCs）至关重要。然而，由于细胞数量有限和骨髓样本稀缺，人类造血干细胞的代谢谱仍然知之甚少。

附：英文原文

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

Author: Lalioti, Maria-Eleni, Romero-Mulero, Mari Carmen, Karabacz, Nomie, Mess, Julian, Demollin, Helen, Rettkowski, Jasmin, Schuldes, Konrad, Mitterer, Michael, Wadle, Carolin, Shoumariyeh, Khalid, Egg, Mirijam, Alfonso-Gonzalez, Carlos, Jcklein, Karin, Schnberger, Katharina, Karantzelis, Nikolaos, Reisig, Gregor, Aktories, Philipp, Mayer, Isabella M., Tsoukala, Ioanna, Schffer, Alexander, Tirado-Gonzalez, Irene, Dugourd, Aurlien, Braun, Lukas M., Silva-Rego, Beatriz, Jones, Michael-Jason, Kierdorf, Katrin, Saez-Rodriguez, Julio, Reising, Kilian, Walter, Sebastian Gottfried, Medyouf, Hind, Hilgers, Valrie, Ghiaur, Gabriel, Zeiser, Robert, Karpova, Darja, Renders, Simon, Gravius, Sascha, Buescher, Joerg, Cabezas-Wallscheid, Nina

Issue&Volume: 2025-07-15

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.

DOI: 10.1038/s41556-025-01709-7

Source: https://www.nature.com/articles/s41556-025-01709-7