Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells
Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells
复制标题
DOI：
10.1016/j.stem.2007.10.008
复制
发表时间：
2007-12-01
期刊：
影响因子：
23.9
通讯作者：
Jacobsen, Sten Eirik W.
中科院分区：
文献类型：
--
作者：
Qian, Hong;Buza-Vidas, Natalija;Jacobsen, Sten Eirik W.
细胞因子在造血干细胞（HSC）调控中的作用仍然知之甚少。在此，我们证明，血小板生成素（THPO）及其受体，MPL，是至关重要的参与出生后稳态HSC的维持，反映在一个150倍的减少HSC在成年Thpo（-1-）小鼠。此外，而THPO和MPL证明胎儿HSC扩增不需要，HSC扩增移植后是高度MPL和THPO依赖。THPO在出生后HSC维持中的独特作用伴随着Thpo-1-小鼠中HSC细胞周期动力学的加速和细胞周期蛋白依赖性激酶抑制剂p57（KiP 2）和p19（INK 4D）以及多种Hox转录因子的表达减少。虽然也被预测为HSC活力因子，但BCL 2未能拯救Thpo（-1-）小鼠的HSC缺陷。因此，THPO调节移植后HSC扩增以及维持成体静止HSC，对于避免出生后HSC衰竭至关重要。
The role of cytokines, in regulation of hematopoietic stem cells (HSCs) remains poorly understood. Herein we demonstrate that thrombopoietin (THPO) and its receptor, MPL, are critically involved in postnatal steady-state HSC maintenance, reflected in a 150-fold reduction of HSCs in adult Thpo(-1-) mice. Further, whereas THPO and MPL proved not required for fetal HSC expansion, HSC expansion posttransplantation was highly MPL and THPO dependent. The distinct role of THPO in postnatal HSC maintenance is accompanied by accelerated HSC cell-cycle kinetics in Thpo-1- mice and reduced expression of the cyclin-dependent kinase inhibitors p57(KiP2) and p19(INK4D) as well as multiple Hox transcription factors. Although also predicted to be an HSC viability factor, BCL2 failed to rescue the HSC deficiency of Thpo(-1-) mice. Thus, THPO regulates posttransplantation HSC expansion as well as the maintenance of adult quiescent HSCs, of critical importance to avoid postnatal HSC exhaustion.