Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, Department of Basic and Translational Sciences, University of Pennsylvania, Philadelphia, PA, United States.
Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Centre for Cardiovascular Science, Queen's Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, United Kingdom; National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden Germany, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Mol Aspects Med. 2021 Feb;77:100923. doi: 10.1016/j.mam.2020.100923. Epub 2020 Nov 5.
Hematopoietic stem cells (HSC) lie at the center of the hematopoiesis process, as they bear capacity to self-renew and generate all hematopoietic lineages, hence, all mature blood cells. The ability of HSCs to recognize systemic infection or inflammation or other forms of peripheral stress, such as blood loss, is essential for demand-adapted hematopoiesis. Also of critical importance for HSC function, specific metabolic cues (e.g., associated with changes in energy or O levels) can regulate HSC function and fate decisions. In this regard, the metabolic adaptation of HSCs facilitates their switching between different states, namely quiescence, self-renewal, proliferation and differentiation. Specific metabolic alterations in hematopoietic stem and progenitor cells (HSPCs) have been linked with the induction of trained myelopoiesis in the bone marrow as well as with HSPC dysfunction in aging and clonal hematopoiesis of indeterminate potential (CHIP). Thus, HSPC function is regulated by both immunologic/inflammatory and metabolic cues. The immunometabolic control of HSPCs and of hematopoiesis is discussed in this review along with the translational implications thereof, that is, how metabolic pathways can be therapeutically manipulated to prevent or reverse HSPC dysfunction or to enhance or attenuate trained myelopoiesis according to the needs of the host.
造血干细胞（HSC）位于造血过程的中心，因为它们具有自我更新和产生所有造血谱系的能力，因此也能生成所有成熟的血细胞。HSC 识别全身感染或炎症或其他形式的外周应激（如失血）的能力对于适应需求的造血至关重要。同样对 HSC 功能至关重要的是，特定的代谢线索（例如，与能量或 O 水平的变化相关的线索）可以调节 HSC 功能和命运决策。在这方面，HSC 的代谢适应促进了它们在不同状态（即静止、自我更新、增殖和分化）之间的转换。造血干细胞和祖细胞（HSPC）中的特定代谢改变与骨髓中受过训练的髓样生成以及衰老和不确定潜能的克隆性造血（CHIP）中 HSPC 功能障碍有关。因此，HSPC 的功能受到免疫/炎症和代谢线索的共同调控。本文综述了 HSPC 及其造血的免疫代谢调控，以及由此产生的转化意义，即根据宿主的需要，如何通过代谢途径的治疗性操作来预防或逆转 HSPC 功能障碍，或增强或减弱受过训练的髓样生成。
