Chiba Shigeru
Department of Cell Therapy and Transplantation Medicine, University of Tokyo Hospital.
Nihon Rinsho. 2008 Mar;66(3):439-43.
Hematopoietic stem cells (HSCs) maintain themselves over cell divisions (self-renewal) and produce all kinds of blood cells (multi-potency). Depletion of these cells eventually causes hematopoietic failure, while deregulated HSC division causes development of myeloproliferative disorders and leukemias. HSCs can be prospectively purified to nearly homogeneity in mice, but such a high-level purification has not been achieved in humans. HSCs are localized to an anatomical place called 'niche'. Specialized osteoblasts arrayed on the endosteum of cavernous bone and sinusoidal endothelial cells located at the distant position from the endosteum are the two representative candidates of such an HSC niche. A number of adhesion molecules and signaling molecules are thought to comprise the niche-HSC synapse. HSCs divide only once in 1-2 months. Both environmental signaling from the niche and HSC-autonomous molecular programs contribute to the quiescent state of HSCs, which is essential for the maintenance of HSC self-renewal capacity and homeostasis of blood production.
造血干细胞(HSCs)通过细胞分裂维持自身(自我更新)并产生各类血细胞(多能性)。这些细胞的耗竭最终会导致造血功能衰竭,而造血干细胞的异常分裂则会引发骨髓增殖性疾病和白血病。在小鼠中,造血干细胞可以被前瞻性地纯化至近乎同质,但在人类中尚未实现如此高水平的纯化。造血干细胞定位于一个名为“龛位”的解剖位置。排列在海绵骨骨内膜上的特化成骨细胞和位于远离骨内膜位置的窦状内皮细胞是这种造血干细胞龛位的两个代表性候选者。许多黏附分子和信号分子被认为构成了龛位 - 造血干细胞突触。造血干细胞每1 - 2个月仅分裂一次。来自龛位的环境信号和造血干细胞自主分子程序都有助于造血干细胞的静止状态,这对于维持造血干细胞的自我更新能力和血液生成的稳态至关重要。