Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York, NY, USA.
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, NY, USA.
Nat Rev Mol Cell Biol. 2019 May;20(5):303-320. doi: 10.1038/s41580-019-0103-9.
The haematopoietic stem cell (HSC) microenvironment in the bone marrow, termed the niche, ensures haematopoietic homeostasis by controlling the proliferation, self-renewal, differentiation and migration of HSCs and progenitor cells at steady state and in response to emergencies and injury. Improved methods for HSC isolation, driven by advances in single-cell and molecular technologies, have led to a better understanding of their behaviour, heterogeneity and lineage fate and of the niche cells and signals that regulate their function. Niche regulatory signals can be in the form of cell-bound or secreted factors and other local physical cues. A combination of technological advances in bone marrow imaging and genetic manipulation of crucial regulatory factors has enabled the identification of several candidate cell types regulating the niche, including both non-haematopoietic (for example, perivascular mesenchymal stem and endothelial cells) and HSC-derived (for example, megakaryocytes, macrophages and regulatory T cells), with better topographical understanding of HSC localization in the bone marrow. Here, we review advances in our understanding of HSC regulation by niches during homeostasis, ageing and cancer, and we discuss their implications for the development of therapies to rejuvenate aged HSCs or niches or to disrupt self-reinforcing malignant niches.
造血干细胞（HSC）在骨髓中的微环境，称为龛，通过控制 HSC 和祖细胞在稳态下的增殖、自我更新、分化和迁移，以及应对紧急情况和损伤，来确保造血稳态。单细胞和分子技术的进步推动了 HSC 的分离方法的改进，这使得人们对其行为、异质性和谱系命运以及调节其功能的龛细胞和信号有了更好的理解。龛调节信号可以是细胞结合或分泌的因子和其他局部物理线索的形式。骨髓成像技术的进步和关键调节因子的遗传操作的结合，使人们能够鉴定出几种调节龛的候选细胞类型，包括非造血细胞（例如，血管周间充质干细胞和内皮细胞）和 HSC 衍生的细胞（例如，巨核细胞、巨噬细胞和调节性 T 细胞），从而更好地了解 HSC 在骨髓中的定位。在这里，我们回顾了龛在稳态、衰老和癌症过程中对 HSC 调节的理解进展，并讨论了它们对开发恢复衰老 HSC 或龛的疗法或破坏自我强化的恶性龛的意义。
