Normal Hematopoiesis Is a Balancing Act of Self-Renewal and Regeneration.
Normal Hematopoiesis Is a Balancing Act of Self-Renewal and Regeneration.
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正常造血是自我更新和再生的平衡行为。
DOI：
10.1101/cshperspect.a035519
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发表时间：
2020
影响因子：
5.4
通讯作者：
Passegué,Emmanuelle
中科院分区：
文献类型：
--
作者：
Olson,OakleyC;Kang,Yoon-A;Passegué,Emmanuelle
造血系统被高度组织起来，以保持其功能的完整性，并满足终生生物的需求。造血干细胞(HSCs)必须在自我更新、分化和血液系统再生之间取得平衡。这是在这些相互竞争的HSC职能之间进行复杂的平衡。尽管HSC在稳定状态下高度静止，但在炎性细胞因子和再生挑战的响应下，HSCs会被激活。这一激活阶段导致许多内源性应激，如复制应激、代谢应激和氧化应激，这些应激可导致肝星状细胞功能衰退、自我更新受损和衰竭。为了应对这些侮辱，造血干细胞使用内置和紧急触发的应激反应机制来维持体内平衡，并防止疾病的发展。在这篇综述中，我们讨论了造血系统如何在稳定状态和应激条件下运作，采取什么策略来维持功能的完整性，以及自我更新和再生之间的平衡放松如何推动恶性转化。
The hematopoietic system is highly organized to maintain its functional integrity and to meet lifelong organismal demands. Hematopoietic stem cells (HSCs) must balance self-renewal with differentiation and the regeneration of the blood system. It is a complex balancing act between these competing HSC functions. Although highly quiescent at steady state, HSCs become activated in response to inflammatory cytokines and regenerative challenges. This activation phase leads to many intrinsic stresses such as replicative, metabolic, and oxidative stress, which can cause functional decline, impaired self-renewal, and exhaustion of HSCs. To cope with these insults, HSCs use both built-in and emergency-triggered stress-response mechanisms to maintain homeostasis and to defend against disease development. In this review, we discuss how the hematopoietic system operates in steady state and stress conditions, what strategies are used to maintain functional integrity, and how deregulation in the balance between self-renewal and regeneration can drive malignant transformation.