[Regulation of Neuro-Microenvironment on Mitochondrial Mass of Hematopoietic Stem and Progenitor Cells]

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Dec;31(6):1838-1844. doi: 10.19746/j.cnki.issn.1009-2137.2023.06.037.
[Article in Chinese]

Abstract

Objective: To study the effects of the neuro-microenvironment on the mass of mitochondria in hematopoietic stem and progenitor cells (HSPC), and to understand the potential mechanisms how nerve regulates HSPC.

Methods: 6-hydroxydopamine (6-OHDA) and capsaicin were used to interfere with the function of sympathetic nerve and nociceptive nerve in mitochondria-GFP reporter mice, respectively. The fluorescence intensity of GFP in bone marrow and spleen was measured by flow cytometry. The GFP median fluorescence intensity (MFI) of HSPC in normal bone marrow and spleen was analyzed and compared. The changes of the mitochondrial mass in HSPCs in each group after denervation were compared.

Results: Hematopoietic stem cells (HSC) had the highest mito-GFP MFI in steady-state (49 793±1 877), and the mito-GFP MFI gradually decreased during the differentiation of HSCs. Compared with control group, pharmaceutical nociceptive denervation significantly increased the mito-GFP MFI of bone marrow multipotent progenitor-1 (MPP1, 50 751±420 vs 44 020±510) and LKS- cells (15 673±65 vs 13 979±103); pharmaceutical sympathetic denervation significantly reduced the mito-GFP MFI of bone marrow LKS+ cells (21 667±351 vs 29 249±973).

Conclusion: Sympathetic and nociceptive nerves can regulate the mass of mitochondria in HSPC and affect the function of HSPCs.

题目: 神经微环境对造血干/祖细胞线粒体数目的调节作用.

目的: 研究神经微环境对造血干/祖细胞(HSPC)线粒体数目的影响,从而揭示造血干/祖细胞受神经调控的潜在机制.

方法: 应用六羟基多巴(6-OHDA)和辣椒素(capsaicin)分别干扰线粒体-绿色荧光蛋白报告鼠(mitochondria-GFP)体内交感神经和伤害性感受神经的功能, 通过流式细胞术对骨髓及脾脏各群造血干/祖细胞GFP荧光强度进行检测。分析比较正常骨髓及脾脏HSPC的GFP平均荧光强度(MFI)。比较药物去除神经作用后的各群HSPC线粒体数目变化.

结果: 在稳态造血中,骨髓造血干细胞(HSC)具有最高的mito-GFP MFI(49 793±1 877)。造血干细胞在谱系分化过程中,mito-GFP MFI逐渐下降。与对照组比较,药物去除伤害性感受神经显著提高骨髓MPP1(multipotent progenitor-1)mito-GFP MFI(50 751±420 vs 44 020±510)和LKS-(Lineage-cKit+Sca1-)细胞mito-GFP MFI(15 673±65 vs 13 979±103);药物去除交感神经显著降低骨髓LKS+(Lineage-cKit+Sca1+)细胞mito-GFP MFI(21 667±351 vs 29 249±973).

结论: 交感神经和伤害性感受神经可调节HSPC线粒体数目,从而影响造血干/祖细胞的功能.

Keywords: hematopoietic stem and progenitor cells; mitochondrion; nociceptive nerves; sympathetic nerve.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • Bone Marrow* / metabolism
  • Cell Differentiation
  • Hematopoietic Stem Cells*
  • Mice
  • Mitochondria
  • Pharmaceutical Preparations / metabolism

Substances

  • Pharmaceutical Preparations