Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA,
Calcif Tissue Int. 2014 Jan;94(1):112-24. doi: 10.1007/s00223-013-9805-8. Epub 2013 Oct 8.
The skeleton serves as the principal site for hematopoiesis in adult terrestrial vertebrates. The function of the hematopoietic system is to maintain homeostatic levels of all circulating blood cells, including myeloid cells, lymphoid cells, red blood cells, and platelets. This action requires the daily production of more than 500 billion blood cells. The vast majority of these cells are synthesized in the bone marrow, where they arise from a limited number of hematopoietic stem cells (HSCs) that are multipotent and capable of extensive self-renewal. These attributes of HSCs are best demonstrated by marrow transplantation, where even a single HSC can repopulate the entire hematopoietic system. HSCs are therefore adult stem cells capable of multilineage repopulation, poised between cell fate choices which include quiescence, self-renewal, differentiation, and apoptosis. While HSC fate choices are in part determined by multiple stochastic fluctuations of cell autonomous processes, according to the niche hypothesis, signals from the microenvironment are also likely to determine stem cell fate. While it had long been postulated that signals within the bone marrow could provide regulation of hematopoietic cells, it is only in the past decade that advances in flow cytometry and genetic models have allowed for a deeper understanding of the microenvironmental regulation of HSCs. In this review, we will highlight the cellular regulatory components of the HSC niche.
在成年陆地脊椎动物中，骨骼是造血的主要部位。造血系统的功能是维持所有循环血细胞（包括髓系细胞、淋巴系细胞、红细胞和血小板）的体内平衡水平。这一作用需要每天生成超过 5000 亿个血细胞。这些细胞中的绝大多数是在骨髓中合成的，它们来自于少数具有多能性和广泛自我更新能力的造血干细胞（HSCs）。骨髓移植最能证明 HSCs 的这些特性，即使是单个 HSC 也可以重新填充整个造血系统。因此，HSCs 是能够多谱系重填充的成体干细胞，处于包括静止、自我更新、分化和凋亡在内的细胞命运选择之间。虽然 HSC 命运选择部分取决于细胞自主过程的多个随机波动，但根据生态位假说，微环境中的信号也可能决定干细胞命运。虽然长期以来人们一直假设骨髓内的信号可以调节造血细胞，但直到过去十年，流式细胞术和遗传模型的进展才使人们更深入地了解了 HSCs 的微环境调节。在这篇综述中，我们将重点介绍 HSC 生态位的细胞调节成分。
