<scp>l</scp> -Carnitine regulates regeneration of human hematopoietic stem and progenitor cells
Abstract
Abstract Understanding how metabolism governs human hematopoietic stem cells (HSCs) function is essential for advancing regenerative therapies, yet direct metabolic profiling of human HSCs has been limited by their extreme scarcity and the technical limitations of conventional methods. Here, we applied a low-input mass spectrometry–based metabolomics platform, optimized for rare cell populations, to generate metabolic profiles of 13 immunophenotypically defined hematopoietic cell types from adult human bone marrow. Using as few as ∼10 000 cells per sample, we detected &gt;80 metabolites and uncovered both conserved metabolic programs in primitive hematopoietic stem and progenitor cells (HSPCs) and lineage-specific metabolic specializations. Of note, we identified l-carnitine–driven fatty acid oxidation as a key metabolic feature supporting HSPC function. Mechanistically, l-carnitine activates the peroxisome proliferator-activated receptor alpha–transcription factor EB signaling axis, promoting mitochondrial metabolism and autophagy to preserve regenerative capacity. Functional assays in primary CD34+ HSPCs derived from healthy donors or patients with aplastic anemia confirm that l-carnitine supplementation improves stem cell function ex vivo and in vivo. This work provides a foundation for human hematopoietic metabolism and reveals a targetable metabolic circuit governing HSPC regenerative fitness with therapeutic potential for improving stem cell–based interventions.
Article Details
Authors (22)
Honglin Duan
1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Bohong Wang
Yawei Zheng
1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Yanling Lv
Ting Lu
Centre for Future Materials, School of Science, Engineering and Digital Technologies
Haoyuan Li
Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Biomedical Engineering and Imaging Institute, Friedman Brain Institute
Pujiao Li
1State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Ruonan Li
State Key Laboratory of Experimental Hematology, Tianjin, China
Xiaowei Xie
Zining Yang
1State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Guohuan Sun
1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Xiangnan Zhao
1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Meng Yang
Yicheng He
Chang Xu
Department of Chemistry, Anhui University, 111 Jiulong Road, Hefei 230601, P. R. China
Shuangshuang Pu
1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Linmin Zhang
1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
Jun Shi
Erlie Jiang
Tao Cheng
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Jiangsu Key Laboratory of Advanced Negative Carbon Technologies
Zeping Hu
Hui Cheng