Department of Oncology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 8/2 Trubetskaya Str, Moscow, 119991, Russia.
Department of Human Anatomy and Histology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 8/2 Trubetskaya Str, Moscow, 119991, Russia.
Stem Cell Res Ther. 2024 Nov 6;15(1):401. doi: 10.1186/s13287-024-04008-4.
Hematopoiesis within the bone marrow (BM) is a complex and tightly regulated process predominantly influenced by immune factors. Aging, diabetes, and obesity are significant contributors to BM niche damage, which can alter hematopoiesis and lead to the development of clonal hematopoiesis of intermediate potential (CHIP). Genetic/epigenetic alterations during aging could influence BM niche reorganization for hematopoiesis or clonal hematopoiesis. CHIP is driven by mutations in genes such as Tet2, Dnmt3a, Asxl1, and Jak2, which are associated with age-related hematological malignancies.
This literature review aims to provide an updated exploration of the functional aspects of BM niche cells within the hematopoietic microenvironment in the context of age-related hematological malignancies. The review specifically focuses on how immunological stressors modulate different signaling pathways that impact hematopoiesis.
An extensive review of recent studies was conducted, examining the roles of various BM niche cells in hematopoietic stem cell (HSC) trafficking and the development of age-related hematological malignancies. Emphasis was placed on understanding the influence of immunological stressors on these processes.
Recent findings reveal a significant microheterogeneity and temporal stochasticity of niche cells across the BM during hematopoiesis. These studies demonstrate that niche cells, including mesenchymal stem cells, osteoblasts, and endothelial cells, exhibit dynamic interactions with HSCs, significantly influenced by the BM microenvironment as the age increases. Immunosurveillance plays a crucial role in maintaining hematopoietic homeostasis, with alterations in immune signaling pathways contributing to the onset of hematological malignancies. Novel insights into the interaction between niche cells and HSCs under stress/aging conditions highlight the importance of niche plasticity and adaptability.
The involvement of age-induced genetic/epigenetic alterations in BM niche cells and immunological stressors in hematopoiesis is crucial for understanding the development of age-related hematological malignancies. This comprehensive review provides new insights into the complex interplay between niche cells and HSCs, emphasizing the potential for novel therapeutic approaches that target niche cell functionality and resilience to improve hematopoietic outcomes in the context of aging and metabolic disorders.
This review introduces novel concepts regarding the plasticity and adaptability of BM niche cells in response to immunological stressors and epigenetics. It proposes that targeted therapeutic strategies aimed at enhancing niche cell resilience could mitigate the adverse effects of aging, diabetes, and obesity on hematopoiesis and clonal hematopoiesis. Additionally, the review suggests that understanding the precise temporal and spatial dynamics of niche-HSC interactions and epigenetics influence may lead to innovative treatments for age-related hematological malignancies.
骨髓（BM）中的造血是一个复杂而受严格调控的过程，主要受免疫因素的影响。衰老、糖尿病和肥胖是骨髓龛损伤的重要因素，这可能改变造血并导致中间潜能克隆性造血（CHIP）的发展。衰老过程中的遗传/表观遗传改变可能会影响造血或克隆性造血的骨髓龛重组。CHIP 是由 Tet2、Dnmt3a、Asxl1 和 Jak2 等基因的突变驱动的，这些基因与年龄相关的血液恶性肿瘤有关。
本文献综述旨在提供对衰老相关血液恶性肿瘤背景下造血微环境中骨髓龛细胞功能方面的最新探索。本综述特别关注免疫应激如何调节影响造血的不同信号通路。
对最近的研究进行了广泛的回顾，研究了各种骨髓龛细胞在造血干细胞（HSC）迁移和衰老相关血液恶性肿瘤发展中的作用。重点是了解免疫应激对这些过程的影响。
最近的研究结果表明，在造血过程中，骨髓中的龛细胞具有显著的微异质性和时间随机性。这些研究表明，龛细胞，包括间充质干细胞、成骨细胞和内皮细胞，与 HSC 之间存在动态相互作用，随着年龄的增长，骨髓微环境对其有显著影响。免疫监视在维持造血稳态方面起着至关重要的作用，免疫信号通路的改变导致血液恶性肿瘤的发生。在应激/衰老条件下，龛细胞与 HSC 之间相互作用的新见解强调了龛细胞可塑性和适应性的重要性。
年龄诱导的遗传/表观遗传改变在骨髓龛细胞和造血中的免疫应激中的参与对于理解衰老相关血液恶性肿瘤的发展至关重要。本综述提供了关于龛细胞和 HSC 之间复杂相互作用的新见解，强调了针对龛细胞功能和弹性的靶向治疗策略的潜力，以改善衰老和代谢紊乱背景下的造血结果。
本综述介绍了关于骨髓龛细胞对免疫应激和表观遗传学的可塑性和适应性的新概念。它提出，旨在增强龛细胞弹性的靶向治疗策略可能会减轻衰老、糖尿病和肥胖对造血和克隆性造血的不利影响。此外，该综述还表明，了解龛-HSC 相互作用和表观遗传学影响的精确时空动态可能会为衰老相关血液恶性肿瘤的创新治疗提供思路。
