Columbia Stem Cell Initiative, Department of Genetics and Development, Columbia University, New York, NY, USA.
Nat Rev Immunol. 2024 Aug;24(8):596-613. doi: 10.1038/s41577-024-00998-7. Epub 2024 Mar 11.
Definitive haematopoiesis is the process by which haematopoietic stem cells, located in the bone marrow, generate all haematopoietic cell lineages in healthy adults. Although highly regulated to maintain a stable output of blood cells in health, the haematopoietic system is capable of extensive remodelling in response to external challenges, prioritizing the production of certain cell types at the expense of others. In this Review, we consider how acute insults, such as infections and cytotoxic drug-induced myeloablation, cause molecular, cellular and metabolic changes in haematopoietic stem and progenitor cells at multiple levels of the haematopoietic hierarchy to drive accelerated production of the mature myeloid cells needed to resolve the initiating insult. Moreover, we discuss how dysregulation or subversion of these emergency myelopoiesis mechanisms contributes to the progression of chronic inflammatory diseases and cancer.
确定性造血是造血干细胞在骨髓中生成所有造血细胞谱系的过程。尽管在健康状态下受到高度调节以维持稳定的血细胞输出,但造血系统能够对外界挑战进行广泛的重塑,优先产生某些细胞类型而牺牲其他类型。在这篇综述中,我们考虑了急性损伤(如感染和细胞毒性药物诱导的骨髓清除)如何在造血层次结构的多个水平上引起造血干细胞和祖细胞的分子、细胞和代谢变化,以驱动成熟髓样细胞的加速产生,从而解决起始损伤。此外,我们还讨论了这些应急性髓样细胞生成机制的失调或颠覆如何导致慢性炎症性疾病和癌症的进展。
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