State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Department of Pharmacology & Regenerative Medicine, University of Illinois Chicago, Chicago, IL, United States.
Front Immunol. 2024 Oct 17;15:1425585. doi: 10.3389/fimmu.2024.1425585. eCollection 2024.
The differentiation of hematopoietic cells is significantly affected by cell metabolic activity. However, despite increasing interest in this field, there has been no comprehensive investigation of the metabolic functions of human hematopoietic cells during specific phases of differentiation. Thus, this study was conducted to develop a method for comparing hematopoietic cell lineage differentiation based on the metabolic functions of the cell. The metabolic activity of human umbilical cord-derived hematopoietic cells was examined during various phases of differentiation, specifically, hematopoietic stem cells (HSCs), hematopoietic progenitor cells, and differentiated blood cells. This approach was used to develop comprehensive metabolic maps corresponding to the different stages.
HSCs were found to have robust fatty acid (FA) synthesis, FA oxidation, pentose phosphate pathway (PPP) activity, and glucose uptake, shown by their significantly higher expression of ACAC, CPT1A, G6PD, and GLUT1 as compared to differentiated pluripotent progenitor cells, common myeloid progenitors, megakaryocyte erythroid progenitors, lympho-myeloid primed progenitors, and granulocyte-macrophage progenitor cell populations. In monocytic differentiation, higher levels of ACAC, ASS1, ATP5A, CPT1A, G6PD, GLUT1, IDH2, PRDX2, and HK1 protein expression were evident in classical and intermediate monocytes relative to non-classical monocytes, consistent with high anabolic and catabolic levels. Compared with myelocytes and mature cells, the meta-myelocyte and pro-myelocyte populations of granulocytes show significantly elevated levels of ACAC, ASS1, ATP5A, CPT1A, G6PD, IDH2, PRDX2, and HK. In contrast to naïve and regulatory B cells, pro-B cells had higher levels of oxidative phosphorylation, while regulatory B cells showed greater PPP activity, glucose uptake, and tricarboxylic acid cycle activity. The analyses of T cells also indicated significantly higher ACAC, ASS1, ATP5A, CPT1A, G6PD, GLUT1, IDH2, PRDX2, and HK1 expression levels in CD4+ populations compared with CD8+ populations.
The results provide comprehensive analytical methods and reference values for future systematic studies into the metabolic functions of various cord blood-derived hematopoietic cell populations in different pathological or physiological conditions. These findings could also contribute to research on the connection between cellular metabolism and cancer or aging.
造血细胞的分化受细胞代谢活性的显著影响。然而，尽管人们对这一领域越来越感兴趣，但迄今为止，还没有对人类造血细胞在特定分化阶段的代谢功能进行全面的研究。因此，本研究旨在开发一种基于细胞代谢功能比较造血细胞谱系分化的方法。检测了人脐带血来源的造血细胞在不同分化阶段的代谢活性，具体为造血干细胞（HSCs）、造血祖细胞和分化的血细胞。采用该方法构建了相应的综合代谢图谱。
与分化的多能祖细胞、共同髓系祖细胞、巨核细胞-红细胞祖细胞、淋巴-髓系前体细胞和粒细胞-巨噬细胞祖细胞群体相比，HSCs 表现出更高的 ACAC、CPT1A、G6PD 和 GLUT1 表达水平，表明其具有强大的脂肪酸（FA）合成、FA 氧化、戊糖磷酸途径（PPP）活性和葡萄糖摄取能力。在单核细胞分化过程中，经典单核细胞和中间单核细胞中 ACAC、ASS1、ATP5A、CPT1A、G6PD、GLUT1、IDH2、PRDX2 和 HK1 蛋白表达水平较高，而非经典单核细胞中这些蛋白表达水平较低，这与高合成代谢和分解代谢水平一致。与中幼粒细胞和成熟细胞相比，粒细胞的原始粒细胞和早幼粒细胞群体中 ACAC、ASS1、ATP5A、CPT1A、G6PD、IDH2、PRDX2 和 HK 表达水平显著升高。与幼稚 B 细胞和调节性 B 细胞相比，前 B 细胞具有更高的氧化磷酸化水平，而调节性 B 细胞则表现出更高的 PPP 活性、葡萄糖摄取和三羧酸循环活性。T 细胞分析也表明 CD4+群体中 ACAC、ASS1、ATP5A、CPT1A、G6PD、GLUT1、IDH2、PRDX2 和 HK1 的表达水平明显高于 CD8+群体。
本研究为未来在不同病理或生理条件下对各种脐带血来源造血细胞群体的代谢功能进行系统研究提供了全面的分析方法和参考值。这些发现也可能有助于研究细胞代谢与癌症或衰老之间的联系。
