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糖尿病驱动的造血重塑与代谢记忆

武艺雯^1,2,3, 董芳^1,2,3, 胡晓霞^4,*

¹中国医学科学院血液病医院(中国医学科学院血液学研究所)，血液与健康全国重点实验室，血液系统疾病国家临床医学研究中心，细胞生态海河实验室，天津 300020；²天津医学健康研究院，天津 301600；³北京协和医学院干细胞与再生医学系，天津 300020；⁴上海交通大学医学院附属瑞金医院血液科，上海血液学研究所，组学与疾病全国重点实验室，国家转化医学 研究中心，上海 200025

摘要

糖尿病(diabetes mellitus)是一种以慢性高血糖为特征的代谢性疾病，可引发心血管疾病、肾病、视网膜病变及神经病变等多系统并发症。骨髓及造血干/祖细胞(hematopoietic stem and progenitor cells, HSPCs)在糖尿病病理过程中不仅是代谢紊乱的受害者，同时也是慢性炎症和组织损伤的重要驱动因素。长期高糖显著破坏HSPCs骨髓微环境稳态，导致HSPCs数量减少、动员障碍及分化命运偏倚，造血系统由维持组织修复和免疫稳态的保护者转变为促炎性造血的“始作俑者”。糖尿病可诱导HSPCs及其微环境支持细胞发生代谢重编程与表观遗传重塑。异常代谢与表观遗传调控相互作用，重塑HSPCs转录程序，形成稳定的炎症性造血表型。此外，糖尿病相关的训练免疫使HSPCs获得促炎记忆，并将其向后代髓系细胞传递，从而构成连接代谢记忆与慢性炎症的重要机制。本文系统综述糖尿病状态下造血细胞数量与功能异常，以及代谢重编程与表观遗传调控在造血失衡中的作用，聚焦糖尿病相关造血重塑和代谢记忆的研究进展，旨在从造血系统角度理解糖尿病诱导全身多组织改变的病理生理学过程，为探索糖尿病并发症的潜在造血干预靶点提供参考。

关键词： 糖尿病; 骨髓; 造血干细胞; 动员; 表观遗传; 代谢重编程

Diabetes-driven hematopoietic remodeling and metabolic memory

WU Yi-Wen^1,2,3, DONG Fang^1,2,3, HU Xiao-Xia^4,*

¹Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Blood and Health, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Tianjin 300020, China；²Tianjin Institutes of Health Science, Tianjin 301600, China；³Department of Stem Cell and Regenerative Medicine, Peking Union Medical College, Tianjin 300020, China；⁴Hematology Department of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai 200025, China

Abstract

Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia and is accompanied by a range of complications affecting the cardiovascular system, kidneys, retina, and nervous system. In the context of diabetes, the bone marrow (BM) and hematopoietic stem and progenitor cells (HSPCs) are not only targets of metabolic dysregulation, but also play an active role in driving chronic inflammation and tissue damage. Prolonged hyperglycemia markedly disrupts HSPC bone marrow niche homeostasis, leading to decreased HSPC numbers, impaired mobilization, and biased differentiation. As a result, the hematopoietic system shifts from supporting tissue repair and immune homeostasis to driving pro-inflammatory hematopoiesis. Diabetes induces metabolic reprogramming and epigenetic remodeling in HSPCs, as well as in supportive cells within the BM niche. Aberrant metabolic states interact with epigenetic regulation to reshape transcriptional programs in HSPCs, thereby establishing a stable inflammatory hematopoietic phenotype. In addition, diabetes-associated trained immunity enables HSPCs to acquire pro-inflammatory memory and transmit this bias to their myeloid progeny, providing a mechanistic link between metabolic memory and chronic inflammation. This review systematically summarizes abnormalities in the number and function of hematopoietic cells under diabetic conditions, as well as the roles of metabolic reprogramming and epigenetic regulation in hematopoietic imbalance. It focuses on recent progress in diabetes-associated hematopoietic remodeling and metabolic memory, aiming to provide a hematopoietic perspective for understanding the pathophysiological processes underlying diabetes-induced multi-organ alterations and to offer a reference for exploring potential hematopoietic intervention targets for diabetic complications.

Key words: diabetes mellitus; bone marrow; hematopoietic stem cells; mobilization; epigenetics; metabolic reprogramming

收稿日期：　　录用日期：

通讯作者：胡晓霞　　E-mail:

DOI: 10.13294/j.aps.2026.0076

引用本文：

武艺雯, 董芳, 胡晓霞. 糖尿病驱动的造血重塑与代谢记忆[J]. 生理学报 2026; 78 (4): 889-903.

WU Yi-Wen, DONG Fang, HU Xiao-Xia. Diabetes-driven hematopoietic remodeling and metabolic memory. Acta Physiol Sin 2026; 78 (4): 889-903 (in Chinese with English abstract).