当期文章

红细胞分化发育及调控机制与转化应用研究进展

周硕¹, 赵欣滢¹, 刘悦华², 邓悦林¹, 李娜¹, 高晓飞², 李湘盈^1,*

¹膜生物学全国重点实验室，北京大学生命科学学院，北大-清华生命科学联合中心，北京 100871；²西湖大学未来产业研究中心，杭州 310030

摘要

红细胞通过介导氧气运输支持组织氧依赖性能量代谢，是维持机体代谢稳态的关键功能细胞，其分化与发育过程受多层级调控网络的精密协调，对造血系统稳态具有决定性作用。尽管近年来红系发育的关键调控因子与信号通路已得到广泛解析，但其在发育阶段转换、应激响应及疾病状态下的整合调控机制仍有待系统梳理。本文围绕红细胞分化发育的结构基础、发育程序及其调控逻辑进行综述。首先，从膜骨架入手，概述红细胞的结构特征及其时空组装与调控机制；其次，总结稳态与应激条件下红细胞生成的发育轨迹及其阶段特异性特征；在此基础上，从转录调控、表观遗传修饰、代谢重编程及造血微环境信号等层面，整合解析红细胞生成的多层级调控网络；进一步，以典型红细胞相关疾病为切入点，探讨关键调控通路失衡与疾病发生发展的内在联系；最后，评述红细胞在体外生成、药物递送、免疫调控及再生医学等领域的转化进展及其关键瓶颈。本文旨在构建红细胞分化发育的整合性认知框架，为相关疾病机制研究及临床转化提供理论依据与研究方向。

关键词： 红细胞发育; 红细胞分化调控; 红细胞疾病; 红细胞转化应用

Erythroid differentiation: regulatory mechanisms and translational applications

ZHOU Shuo¹, ZHAO Xin-Ying¹, LIU Yue-Hua², DENG Yue-Lin¹, LI Na¹, GAO Xiaofei², LEE Hsiang-Ying^1,*

¹State Key Laboratory of Membrane Biology, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China；²Research Center for Industries of the Future, Westlake University, Hangzhou 310030, China

Abstract

Erythrocytes support tissue oxygen-dependent energy metabolism by enabling oxygen transport and are essential for maintaining metabolic homeostasis. Their differentiation and development are orchestrated by multilayered regulatory networks that play a decisive role in sustaining hematopoietic homeostasis. Although key regulators and signaling pathways governing erythropoiesis have been extensively characterized, how these mechanisms are integrated across developmental transitions, stress responses, and disease states remains incompletely understood. Here, we provide a comprehensive overview of the structural basis, developmental programs, and regulatory logic of erythropoiesis. We first summarize the structural features of erythrocytes, with a focus on the membrane skeleton and its spatiotemporal assembly and relevant regulatory mechanisms. We then outline the developmental trajectories and stage-specific characteristics of erythropoiesis under both steady-state and stress conditions. Building on this framework, we integrate current knowledge on the multilayered regulatory networks governing erythropoiesis, including transcriptional control, epigenetic regulation, metabolic reprogramming, and signals from the hematopoietic microenvironment. Furthermore, using representative erythrocyte-related disorders as a lens, we discuss how dysregulation of these pathways contributes to disease pathogenesis. Finally, we highlight recent advances and key challenges in the translational applications of erythrocytes, including in vitro generation, drug delivery, immunomodulation, and regenerative medicine. This review aims to establish an integrated conceptual framework for erythroid development and to provide insights for future mechanistic studies and clinical translation.

Key words: erythropoiesis; regulation of erythroid differentiation; erythrocyte-related diseases; RBC translational applications

收稿日期：　　录用日期：

通讯作者：李湘盈　　E-mail:

DOI: 10.13294/j.aps.2026.0079

引用本文：

周硕, 赵欣滢, 刘悦华, 邓悦林, 李娜, 高晓飞, 李湘盈. 红细胞分化发育及调控机制与转化应用研究进展[J]. 生理学报 2026; 78 (4): 762-788.

ZHOU Shuo, ZHAO Xin-Ying, LIU Yue-Hua, DENG Yue-Lin, LI Na, GAO Xiaofei, LEE Hsiang-Ying. Erythroid differentiation: regulatory mechanisms and translational applications. Acta Physiol Sin 2026; 78 (4): 762-788 (in Chinese with English abstract).