Young Kaylene M, Bartlett Perry F, Coulson Elizabeth J
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
J Neurosci Res. 2006 Jan;83(1):39-49. doi: 10.1002/jnr.20702.
The number of cells generated by a proliferating stem or precursor cell can be influenced both by proliferation and by the degree of cell death/survival of the progeny generated. In this study, the extent to which cell survival controls progenitor number was examined by comparing the growth characteristics of neurosphere cultures derived from mice lacking genes for the death-inducing Bcl-2 homologue Hara Kiri (Hrk), apoptosis-associated protein 1 (Apaf1), or the prosurvival nuclear factor-kappaB (NFkappaB) subunits p65, p50, or c-rel. We found no evidence that Hrk or Apaf1, and by inference the mitochondrial cell death pathway, are involved in regulating the number of neurosphere-derived progeny. However, we identified the p65p50 NFkappaB dimer as being required for the normal growth and expansion of neurosphere cultures. Genetic loss of both p65 and p50 NFkappaB subunits resulted in a reduced number of progeny but an increased proportion of neurons. No effect on cell survival was observed. This suggests that the number and fate of neural progenitor cells are more strongly regulated by cell cycle control than survival.
增殖的干细胞或前体细胞产生的细胞数量，会受到增殖以及所产生子代细胞死亡/存活程度的影响。在本研究中，通过比较源自缺乏促死亡Bcl-2同源物Hara Kiri（Hrk）、凋亡相关蛋白1（Apaf1）或促存活核因子-κB（NFκB）亚基p65、p50或c-rel基因的小鼠的神经球培养物的生长特性，来检测细胞存活对祖细胞数量的控制程度。我们没有发现证据表明Hrk或Apaf1以及由此推断的线粒体细胞死亡途径参与调节神经球来源的子代细胞数量。然而，我们确定p65p50 NFκB二聚体是神经球培养物正常生长和扩增所必需的。p65和p50 NFκB亚基的基因缺失导致子代细胞数量减少，但神经元比例增加。未观察到对细胞存活的影响。这表明神经祖细胞的数量和命运受细胞周期控制的调节比受存活的调节更强。
