Eaves Connie J
Terry Fox Laboratory, British Columbia Cancer Agency Vancouver, BC, Canada; and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Blood. 2015 Apr 23;125(17):2605-13. doi: 10.1182/blood-2014-12-570200. Epub 2015 Mar 11.
Hematopoietic stem cell (HSC) research took hold in the 1950s with the demonstration that intravenously injected bone marrow cells can rescue irradiated mice from lethality by reestablishing blood cell production. Attempts to quantify the cells responsible led to the discovery of serially transplantable, donor-derived, macroscopic, multilineage colonies detectable on the spleen surface 1 to 2 weeks posttransplant. The concept of self-renewing multipotent HSCs was born, but accompanied by perplexing evidence of great variability in the outcomes of HSC self-renewal divisions. The next 60 years saw an explosion in the development and use of more refined tools for assessing the behavior of prospectively purified subsets of hematopoietic cells with blood cell-producing capacity. These developments have led to the formulation of increasingly complex hierarchical models of hematopoiesis and a growing list of intrinsic and extrinsic elements that regulate HSC cycling status, viability, self-renewal, and lineage outputs. More recent examination of these properties in individual, highly purified HSCs and analyses of their perpetuation in clonally generated progeny HSCs have now provided definitive evidence of linearly transmitted heterogeneity in HSC states. These results anticipate the need and use of emerging new technologies to establish models that will accommodate such pluralistic features of HSCs and their control mechanisms.
造血干细胞（HSC）研究始于20世纪50年代，当时有研究表明，静脉注射骨髓细胞可通过重建血细胞生成，使受辐照小鼠免于死亡。为了量化起作用的细胞，人们进行了相关尝试，结果发现，在移植后1至2周，可在脾脏表面检测到可连续移植、源自供体的宏观多谱系集落。自我更新多能造血干细胞的概念由此诞生，但同时也出现了令人困惑的证据，表明造血干细胞自我更新分裂的结果存在很大差异。在接下来的60年里，用于评估具有血细胞生成能力的造血细胞前瞻性纯化亚群行为的更精细工具得到了迅猛发展和广泛应用。这些进展促使人们构建出越来越复杂的造血层级模型，并发现了越来越多调节造血干细胞循环状态、活力、自我更新和谱系输出的内在和外在因素。最近，对单个高度纯化的造血干细胞的这些特性进行的研究，以及对其在克隆产生的子代造血干细胞中的延续情况的分析，现已提供了造血干细胞状态线性传递异质性的确凿证据。这些结果预示着需要并使用新兴新技术来建立能够适应造血干细胞及其控制机制这种多元特征的模型。
