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线粒体转移通过 CD47 改变早期红细胞的生物能量特征来介导应激性红细胞生成。

Mitochondria transfer mediates stress erythropoiesis by altering the bioenergetic profiles of early erythroblasts through CD47.

机构信息

Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

International Research Centre for Medical Sciences, Kumamoto University, Kumamoto, Japan.

出版信息

J Exp Med. 2022 Dec 5;219(12). doi: 10.1084/jem.20220685. Epub 2022 Sep 16.

DOI:10.1084/jem.20220685
PMID:36112140
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9485707/
Abstract

Intercellular mitochondria transfer is a biological phenomenon implicated in diverse biological processes. However, the physiological role of this phenomenon remains understudied between erythroblasts and their erythroblastic island (EBI) macrophage niche. To gain further insights into the mitochondria transfer functions, we infused EBI macrophages in vivo into mice subjected to different modes of anemic stresses. Interestingly, we observed the occurrence of mitochondria transfer events from the infused EBI macrophages to early stages of erythroblasts coupled with enhanced erythroid recovery. Single-cell RNA-sequencing analysis on erythroblasts receiving exogenous mitochondria revealed a subset of highly proliferative and metabolically active erythroid populations marked by high expression of CD47. Furthermore, CD47 or Sirpα blockade leads to a decline in both the occurrence of mitochondria transfer events and their mediated erythroid recovery. Hence, these data indicate a significant role of mitochondria transfer in the enhancement of erythroid recovery from stress through the alteration of the bioenergetic profiles via CD47-Sirpα interaction in the early stages of erythroblasts.

摘要

细胞间线粒体转移是一种涉及多种生物学过程的生物学现象。然而,这种现象在红细胞与其成红细胞岛(EBI)巨噬细胞龛之间的生理作用仍研究不足。为了更深入地了解线粒体转移的功能,我们将 EBI 巨噬细胞体内输注到经历不同贫血应激模式的小鼠中。有趣的是,我们观察到从输注的 EBI 巨噬细胞到红细胞早期阶段发生线粒体转移事件,伴随着红细胞生成的增强。对接受外源性线粒体的红细胞进行单细胞 RNA 测序分析显示,一组高度增殖和代谢活跃的红细胞亚群表达高水平的 CD47。此外,CD47 或 Sirpα 阻断导致线粒体转移事件的发生及其介导的红细胞生成恢复减少。因此,这些数据表明,通过 CD47-Sirpα 相互作用改变早期红细胞的生物能量谱,线粒体转移在通过改变生物能量谱增强红细胞对应激的恢复中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/43baa784cb10/JEM_20220685_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/b15c0bbcd555/JEM_20220685_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/4f35b1ee8057/JEM_20220685_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/a1a87e6e2f71/JEM_20220685_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/2c9d02b8354a/JEM_20220685_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/3b7aa4d7c70b/JEM_20220685_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/d320887ef4ea/JEM_20220685_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/10fe32722e8e/JEM_20220685_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/3753180d8984/JEM_20220685_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/1e1cee30ca0f/JEM_20220685_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/7b51f54766f0/JEM_20220685_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/5a0ec763a656/JEM_20220685_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/44e593c42674/JEM_20220685_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/43baa784cb10/JEM_20220685_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/b15c0bbcd555/JEM_20220685_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/4f35b1ee8057/JEM_20220685_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/a1a87e6e2f71/JEM_20220685_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/2c9d02b8354a/JEM_20220685_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/3b7aa4d7c70b/JEM_20220685_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/d320887ef4ea/JEM_20220685_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/10fe32722e8e/JEM_20220685_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/3753180d8984/JEM_20220685_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/1e1cee30ca0f/JEM_20220685_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/7b51f54766f0/JEM_20220685_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/5a0ec763a656/JEM_20220685_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/44e593c42674/JEM_20220685_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6164/9485707/43baa784cb10/JEM_20220685_Fig7.jpg

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