Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, QC, Canada H3A 2B4.
Stem Cells Int. 2012;2012:908183. doi: 10.1155/2012/908183. Epub 2012 Aug 30.
Sirtuin 1 (SIRT1) is a deacetylase that can regulate various biological processes via repression of transcription. Its activity has been linked to the differentiation of neural progenitor cells, although little is known about its function during retinal development. The study described herein was undertaken to evaluate the expression of SIRT1 and its innate inhibitor, DBC1, in retinal tissues and progenitor cells. We found both SIRT1 and DBC1 to be widely expressed in mouse and human retinas, with subtle differences in subcellular distribution of each protein. We further demonstrate that nuclear-localized SIRT1 is only seen in human-derived retinal progenitor cells and not in adult retinas, suggesting that this nuclear localization may be important in retinal development. Moreover, we observed cytoplasmic DBC1 in a subset of progenitor cells as well as in mature ganglion cells, indicating that the progenitor cell subset, which was comprised predominantly of small cells, may represent a population of ganglion cell precursors. Collectively, the data presented in this study provide support for SIRT1 and DBC1 as regulators of retinal development and normal retinal physiology.
Sirtuin 1(SIRT1)是一种去乙酰化酶,可以通过抑制转录来调节各种生物过程。其活性与神经祖细胞的分化有关,尽管在视网膜发育过程中其功能知之甚少。本研究旨在评估 SIRT1 及其天然抑制剂 DBC1 在视网膜组织和祖细胞中的表达。我们发现 SIRT1 和 DBC1 在小鼠和人视网膜中广泛表达,每种蛋白的亚细胞分布存在细微差异。我们进一步证明,核定位的 SIRT1 仅见于人源性视网膜祖细胞,而不存在于成年视网膜中,表明这种核定位可能在视网膜发育中很重要。此外,我们观察到细胞质 DBC1 存在于祖细胞亚群以及成熟的节细胞中,表明祖细胞亚群主要由小细胞组成,可能代表节细胞前体细胞的一个群体。总之,本研究提供的资料支持 SIRT1 和 DBC1 作为视网膜发育和正常视网膜生理的调节剂。