CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Inflammatory memory of stem cells: implications for hematologic diseases.
Inflammatory memory of stem cells: implications for hematologic diseases.
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适应性免疫细胞和固有免疫细胞的免疫记忆已被充分表征,使其在再次遭遇挑战时能够产生增强的反应。然而,直到最近人们才认识到,炎症的非免疫靶细胞,特别是器官特异性干细胞(SC),也表现出对既往炎症暴露的记忆。既往炎症经历会在SC上留下印记,并影响其再生潜力以及对后续炎症打击的反应。这一现象已在造血、肠道和皮肤上皮SC中观察到,对组织稳态、疾病进展和治疗策略具有深远意义。在此,我们扩展并发展SC炎症记忆的概念,并探讨该领域的最新见解。我们讨论对其分子基础的新兴认识及其潜在的临床和生物学意义。炎症记忆由基因位点的时空变化以及受DNA和组蛋白表观遗传修饰、代谢重编程和染色质可及性变化调控的转录所驱动。理解这些机制对于改善血液系统疾病、造血SC移植和细胞免疫治疗的结局至关重要。
Immunological memory in adaptive and innate immune cells is well characterized, enabling enhanced responses upon secondary challenges.
However, it has only been recently appreciated that the nonimmune target cells of inflammation, particularly organ-specific stem cells (SCs), also exhibit memory of previous inflammatory exposures. Previous inflammation experience imprints on the SCs and influences their regenerative potential and responses to subsequent inflammatory insults. This phenomenon has been observed in hematopoietic, intestinal, and skin epithelial SCs, with profound implications for tissue homeostasis, disease progression, and therapeutic strategies.
Herein, we expand and develop the notion of inflammatory memory of SCs and explore recent insights in the field.
We discuss the emerging understanding of the molecular underpinnings and their potential clinical and biological implications. Inflammatory memory is driven by spatiotemporal changes in gene loci and transcription regulated by DNA and histones' epigenetic modifications, metabolic reprogramming, and chromatin accessibility changes. Understanding these mechanisms is critical for improving the outcomes of hematologic diseases, hematopoietic SC transplantation, and cellular immunotherapies.
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