血液幹細胞の代謝地図を作成(Mapping the metabolism of blood stem cells)

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2025-07-15 マックス・プランク研究所

血液幹細胞の代謝地図を作成(Mapping the metabolism of blood stem cells)

Comprehensive analysis of blood stem cells: Using advanced FACS sorting and innovative low-input methods, blood stem cells (HSPCs) and their progenitors were isolated from human bone marrow and examined under different age and disease conditions. By integrating transcriptomic, metabolomic, and lipidomic data, molecular changes during differentiation, aging, and leukemia could be characterized, revealing new approaches to maintain stem cell health.
© MPI of Immunobiology & Epigenetics, Cabezas-Wallscheid

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マックス・プランク研究所とETHチューリッヒの研究チームが、ヒト造血幹細胞(HSC)の代謝マップを初めて構築。トランスクリプトミクス、メタボロミクス、リピドミクスを統合解析し、HSCが休眠状態を保つため代謝活動が低く、コリン濃度が高いことを発見。加齢や白血病ではコリンが減少し、補給により若々しい特性が維持される可能性も示唆。本研究はHSC老化予防や白血病治療への新たな栄養・代謝介入法に道を開く。

<関連情報>

分化、加齢、白血病がヒト骨髄造血幹細胞および前駆細胞の代謝プロファイルを変化させる 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 M. Mayer,Ioanna Tsoukala,Alexander Schäffer,Irene Tirado-Gonzalez,Aurélien Dugourd,Lukas M. Braun,Beatriz Silva-Rego,… Nina Cabezas-Wallscheid
Nature Cell Biology  Published:15 July 2025
DOI:https://doi.org/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.

生物化学工学
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