Conte Maria, Deri Paolo, Isolani Maria Emilia, Mannini Linda, Batistoni Renata
Dipartimento di Biologia, Università di Pisa, I-56017 Ghezzano, Italy.
Dev Biol. 2009 Oct 1;334(1):109-18. doi: 10.1016/j.ydbio.2009.07.010. Epub 2009 Jul 17.
In adult organisms, stem cells are crucial to homeostasis and regeneration of damaged tissues. In planarians, adult stem cells (neoblasts) are endowed with an extraordinary replicative potential that guarantees unlimited replacement of all differentiated cell types and extraordinary regenerative ability. The molecular mechanisms by which neoblasts combine long-term stability and constant proliferative activity, overcoming the impact of time, remain by far unknown. Here we investigate the role of Djmot, a planarian orthologue that encodes a peculiar member of the HSP70 family, named Mortalin, on the dynamics of stem cells of Dugesia japonica. Planarian stem cells and progenitors constitutively express Djmot. Transient Djmot expression in differentiated tissues is only observed after X-ray irradiation. DjmotRNA interference causes inability to regenerate and death of the animals, as a result of permanent growth arrest of stem cells. These results provide the first evidence that an hsp-related gene is essential for neoblast viability and suggest the possibility that high levels of Djmot serve to keep a p53-like protein signaling under control, thus allowing neoblasts to escape cell death programs. Further studies are needed to unravel the molecular pathways involved in these processes.
在成年生物体中,干细胞对于内环境稳态和受损组织的再生至关重要。在涡虫中,成体干细胞(新细胞)具有非凡的复制潜能,可确保所有分化细胞类型的无限替换以及卓越的再生能力。新细胞如何结合长期稳定性和持续增殖活性以克服时间影响的分子机制,目前仍完全未知。在此,我们研究了Djmot的作用,它是涡虫中一个编码HSP70家族特殊成员(名为Mortalin)的直系同源物,对日本三角涡虫干细胞动态的影响。涡虫干细胞和祖细胞持续表达Djmot。仅在X射线照射后,才会在分化组织中观察到短暂的Djmot表达。DjmotRNA干扰导致动物无法再生并死亡,这是干细胞永久性生长停滞的结果。这些结果首次证明了一个与热休克蛋白相关的基因对新细胞的存活至关重要,并表明高水平的Djmot可能有助于控制类似p53的蛋白质信号传导,从而使新细胞逃避细胞死亡程序。需要进一步研究来阐明这些过程中涉及的分子途径。