Proteomic characterization of murine hematopoietic stem progenitor cells reveals dynamic fetal-to-adult changes in metabolic-related pathways.

Yanyu Xiu, Mingfang Xiong, Haoyu Yang, Qianqian Wang, Xiao Zhao, Juan Long, Fei Liang, Nan Liu, Fudong Chen, Meng Gao, Yuying Sun, Ruiwen Fan, Yang Zeng

College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, China; Senior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, 100071, China.College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, China; Senior Department of Hematology, the Fifth Medical Center of PLA General Hospital, Beijing, 100071, China. · pubmed

Paper

Abstract

Hematopoietic stem progenitor cells (HSPCs) give rise to the hematopoietic system, maintain hematopoiesis throughout the lifespan, and undergo molecular and functional changes during their development and aging. The importance of hematopoietic stem cell (HSC) biology has led to their extensive characterization at genomic and transcriptomic levels. However, the proteomics of HSPCs throughout the murine lifetime still needs to be fully completed. Here, using mass spectrometry (MS)-based quantitative proteomics, we report on the dynamic changes in the proteome of HSPCs from four developmental stages in the fetal liver (FL) and the bone marrow (BM), including E14.5, young (2 months), middle-aged (8 months), and aging (18 months) stages. Proteomics unveils highly dynamic protein kinetics during the development and aging of HSPCs. Our data identify stage-specific developmental features of HSPCs, which can be linked to their functional maturation and senescence. Our proteomic data demonstrated that FL HSPCs depend on aerobic respiration to meet their proliferation and oxygen supply demand, while adult HSPCs prefer glycolysis to preserve the HSC pool. By functional assays, we validated the decreased mitochondrial metabolism, glucose uptake, reactive oxygen species (ROS) production, protein synthesis rate, and increased glutathione S-transferase (GST) activity during HSPC development from fetal to adult. Distinct metabolism pathways and immune-related pathways enriched in different HSPC developmental stages were revealed at the protein level. Our study will have broader implications for understanding the mechanism of stem cell maintenance and fate determination and reversing the HSC aging process.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper is relevant to longevity research as it investigates the proteomic changes in hematopoietic stem progenitor cells (HSPCs) throughout different stages of development and aging, which can provide insights into stem cell maintenance and aging processes. However, while it presents solid research on metabolic pathways and their implications for HSC aging, the findings are more incremental rather than groundbreaking, limiting its overall impact on the field.

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