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红细胞去核机制的新见解:从基础到临床应用

New insights into the mechanisms of red blood cell enucleation: From basics to clinical applications.

作者信息

Zhuo Qianli, Zhang Zhaojun, Fang Xiangdong

机构信息

China National Center for Bioinformation Beijing China.

Beijing Institute of Genomics, Chinese Academy of Sciences Beijing China.

出版信息

EJHaem. 2024 Nov 13;5(6):1301-1311. doi: 10.1002/jha2.1051. eCollection 2024 Dec.

DOI:10.1002/jha2.1051
PMID:39691252
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11647694/
Abstract

BACKGROUND

Red blood cell (RBC) enucleation is a crucial step in the process of erythropoiesis. By removing the nucleus, RBCs gain greater flexibility, enabling them to traverse narrow capillaries with ease, thereby enhancing the efficiency of oxygen and carbon dioxide transport. This transformation underscores the intricate balance between cellular structure and function essential for maintaining homeostasis.

TOPIC

This review delves into the multifaceted enucleation process, outlining its complex steps that encompass protein sorting, vesicle trafficking, cytoskeletal remodeling, and apoptosis regulation, while also exploring the potential of enhancing the enucleation rate of RBCs in vitro. We emphasize the intricate regulation of this process, which is orchestrated by multiple factors. This includes transcription factors that meticulously guide protein synthesis and sorting through the modulation of gene expression, as well as non-coding RNAs that play a pivotal role in post-transcriptional regulation during various stages of RBC enucleation. Additionally, macrophages participate in the enucleation process by engulfing and clearing the extruded nuclei, further ensuring the proper development of RBCs. Although many studies have deeply explored the molecular mechanisms of enucleation, the roles of apoptosis and anti-apoptotic processes in RBC enucleation remain incompletely understood.

IMPLICATION

In this review, we aim to comprehensively summarize the RBC enucleation process and explore the progress made in ex vivo RBC generation. In the future, a deeper understanding of the enucleation process could provide significant benefits to patients suffering from anemia and other related conditions.

摘要

背景

红细胞去核是红细胞生成过程中的关键步骤。通过去除细胞核,红细胞获得了更大的灵活性,使其能够轻松穿过狭窄的毛细血管,从而提高氧气和二氧化碳的运输效率。这种转变凸显了维持体内平衡所必需的细胞结构与功能之间的复杂平衡。

主题

本综述深入探讨了多方面的去核过程,概述了其复杂步骤,包括蛋白质分选、囊泡运输、细胞骨架重塑和凋亡调控,同时还探索了在体外提高红细胞去核率的潜力。我们强调这一过程受到多种因素精心调控。这包括通过调节基因表达来精确指导蛋白质合成和分选的转录因子,以及在红细胞去核各个阶段的转录后调控中发挥关键作用的非编码RNA。此外,巨噬细胞通过吞噬和清除挤出的细胞核参与去核过程,进一步确保红细胞的正常发育。尽管许多研究已深入探讨去核的分子机制,但凋亡和抗凋亡过程在红细胞去核中的作用仍未完全了解。

意义

在本综述中,我们旨在全面总结红细胞去核过程,并探索体外红细胞生成方面取得的进展。未来,对去核过程的更深入理解可能会给贫血及其他相关病症的患者带来显著益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76f0/11647694/0c31e2331fab/JHA2-5-1301-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76f0/11647694/0c31e2331fab/JHA2-5-1301-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76f0/11647694/0c31e2331fab/JHA2-5-1301-g001.jpg

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本文引用的文献

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Metabolite and protein shifts in mature erythrocyte under hypoxia.缺氧条件下成熟红细胞中的代谢物和蛋白质变化
iScience. 2024 Feb 23;27(4):109315. doi: 10.1016/j.isci.2024.109315. eCollection 2024 Apr 19.
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Synergistic effect and molecular mechanism of PVA and UM171 in ex vivo expansion of primitive hematopoietic stem cells.PVA 和 UM171 在原代造血干细胞体外扩增中的协同作用及分子机制。
J Cell Biochem. 2024 Jan;125(1):79-88. doi: 10.1002/jcb.30505. Epub 2023 Nov 22.
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HEXIM1 is an essential transcription regulator during human erythropoiesis.
HEXIM1 是人类红细胞生成过程中的一个必需转录调控因子。
Blood. 2023 Dec 21;142(25):2198-2215. doi: 10.1182/blood.2022019495.
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Regulation of erythropoiesis: emerging concepts and therapeutic implications.红细胞生成的调控:新的概念和治疗意义。
Hematology. 2023 Dec;28(1):2250645. doi: 10.1080/16078454.2023.2250645.
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Heterochromatin rewiring and domain disruption-mediated chromatin compaction during erythropoiesis.红细胞生成过程中的异染色质重排和结构域破坏介导的染色质紧缩。
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Comprehensive proteomic analysis reveals dynamic phospho-profiling in human early erythropoiesis.全面蛋白质组学分析揭示人类早期红细胞生成中的动态磷酸化谱。
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Erythroblastic islands foster granulopoiesis in parallel to terminal erythropoiesis.成红细胞岛与终末红细胞生成并行促进粒细胞生成。
Blood. 2022 Oct 6;140(14):1621-1634. doi: 10.1182/blood.2022015724.
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Regulation of Erythropoiesis by the Hypoxia-Inducible Factor Pathway: Effects of Genetic and Pharmacological Perturbations.缺氧诱导因子途径对红细胞生成的调控:遗传和药理学扰动的影响
Annu Rev Med. 2023 Jan 27;74:307-319. doi: 10.1146/annurev-med-042921-102602. Epub 2022 Jun 30.
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