Current Issue

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

Received: 　　Accepted:

Corresponding author: 胡晓霞　　E-mail:

DOI: 10.13294/j.aps.2026.0076

Citing This Article：

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).