Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA; Division of Neonatology, Department of Pediatrics, University of California San Francisco School of Medicine, San Francisco, CA, USA.
Exp Hematol. 2014 Aug;42(8):707-16. doi: 10.1016/j.exphem.2014.06.008. Epub 2014 Jul 8.
The mouse is integral to our understanding of hematopoietic biology. Serving as a mammalian model system, the mouse has allowed for the discovery of self-renewing multipotent stem cells, provided functional assays to establish hematopoietic stem cell identity and function, and has become a tool for understanding the differentiation capacity of early hematopoietic progenitors. The advent of genetic technology has strengthened the use of mouse models for identifying critical pathways in hematopoiesis. Full genetic knockout models, tissue-specific gene deletion, and genetic overexpression models create a system for the dissection and identification of critical cellular and genetic processes underlying hematopoiesis. However, the murine model has also introduced perplexity in understanding developmental hematopoiesis. Requisite in utero development paired with circulation has historically made defining sites of origin and expansion in the murine hematopoietic system challenging. However, the genetic accessibility of the mouse as a mammalian system has identified key regulators of hematopoietic development. Technological advances continue to generate extremely powerful tools that when translated to the murine system provide refined in vivo spatial and temporal control of genetic deletion or overexpression. Future advancements may add the ability of reversible genetic manipulation. In this review, we describe the major contributions of the murine model to our understanding of hematopoiesis.
小鼠是我们理解造血生物学的重要组成部分。作为一种哺乳动物模型系统，小鼠使自我更新的多能干细胞的发现成为可能，提供了功能性测定方法来确定造血干细胞的特性和功能，并成为理解早期造血祖细胞分化能力的工具。遗传技术的出现加强了小鼠模型在鉴定造血过程中关键途径的应用。完全基因敲除模型、组织特异性基因缺失和基因过表达模型为解析和鉴定造血过程中的关键细胞和遗传过程提供了系统。然而，小鼠模型也在理解发育中的造血方面带来了困惑。在历史上，与循环系统相关的必要的宫内发育使得定义小鼠造血系统中的起源和扩展部位具有挑战性。然而，作为一种哺乳动物系统，小鼠的遗传可及性确定了造血发育的关键调节因子。技术进步不断产生极其强大的工具，当将这些工具转化为小鼠系统时，可以提供对遗传缺失或过表达的精细体内时空控制。未来的进展可能会增加可逆遗传操作的能力。在这篇综述中，我们描述了小鼠模型对我们理解造血的主要贡献。
