Dipartimento di Morfologia Umana e Biologia Applicata, Università di Pisa, Pisa, Italy.
J Cell Sci. 2010 Mar 1;123(Pt 5):690-8. doi: 10.1242/jcs.053900. Epub 2010 Feb 2.
Retinoblastoma-associated proteins 46 and 48 (RbAp46 and RbAp48) are factors that are components of different chromatin-modelling complexes, such as polycomb repressive complex 2, the activity of which is related to epigenetic gene regulation in stem cells. To date, no direct findings are available on the in vivo role of RbAp48 in stem-cell biology. We recently identified DjRbAp48 - a planarian (Dugesia japonica) homologue of human RBAP48 - expression of which is restricted to the neoblasts, the adult stem cells of planarians. In vivo silencing of DjRbAp48 induces lethality and inability to regenerate, even though neoblasts proliferate and accumulate after wounding. Despite a partial reduction in neoblast number, we were always able to detect a significant number of these cells in DjRbAp48 RNAi animals. Parallel to the decrease in neoblasts, a reduction in the number of differentiated cells and the presence of apoptotic-like neoblasts were detectable in RNAi animals. These findings suggest that DjRbAp48 is not involved in neoblast maintenance, but rather in the regulation of differentiation of stem-cell progeny. We discuss our data, taking into account the possibility that DjRbAp48 might control the expression of genes necessary for cell differentiation by influencing chromatin architecture.
视网膜母细胞瘤相关蛋白 46 和 48(RbAp46 和 RbAp48)是不同染色质建模复合物的组成部分,如多梳抑制复合物 2,其活性与干细胞中的表观遗传基因调控有关。迄今为止,尚无关于 RbAp48 在干细胞生物学中的体内作用的直接发现。我们最近鉴定了 DjRbAp48——一种扁形动物(日本三角涡虫)与人 RBAP48 的同源物——其表达仅限于成体干细胞的神经嵴细胞。DjRbAp48 的体内沉默会导致死亡和无法再生,尽管神经嵴细胞在受伤后会增殖和积累。尽管神经嵴细胞的数量略有减少,但我们总能在 DjRbAp48 RNAi 动物中检测到大量这些细胞。与神经嵴细胞数量减少平行的是,在 RNAi 动物中可检测到分化细胞数量减少和凋亡样神经嵴细胞的存在。这些发现表明,DjRbAp48 不参与神经嵴细胞的维持,而是参与干细胞后代分化的调节。我们讨论了我们的数据,考虑到 DjRbAp48 可能通过影响染色质结构来控制细胞分化所需基因的表达的可能性。