Bergqvist Cecilia, Jafferali Mohammed Hakim, Gudise Santhosh, Markus Robert, Hallberg Einar
Department of Neurochemistry, Stockholm University, Svante Arrhenius väg 16B, SE-106 91 Stockholm, Sweden.
Department of Neurochemistry, Stockholm University, Svante Arrhenius väg 16B, SE-106 91 Stockholm, Sweden.
Stem Cell Res. 2017 Aug;23:33-38. doi: 10.1016/j.scr.2017.06.008. Epub 2017 Jun 22.
The ability of iPSCs (induced pluripotent stem cells) to generate any cell type in the body makes them valuable tools for cell replacement therapies. However, differentiation of iPSCs can be demanding, slow and variable. During differentiation chromatin is re-organized and silent dense heterochromatin becomes tethered to the nuclear periphery by processes involving the nuclear lamina and proteins of the INM (inner nuclear membrane). The INM protein, Samp1 (Spindle Associated Membrane Protein 1) interacts with Lamin A/C and the INM protein Emerin, which has a chromatin binding LEM (Lap2-Emerin-Man1)-domain. In this paper we investigate if Samp1 can play a role in the differentiation of iPSCs. Samp1 levels increased as differentiating iPSCs started to express Lamin A/C. Interestingly, even under pluripotent culturing conditions, ectopic expression of Samp1 induced a rapid differentiation of iPSCs, of which some expressed the neuronal marker βIII-tubulin already after 6days. This suggests that Samp1 is involved in early differentiation of iPSCs and could potentially be explored as a tool to promote progression of the differentiation process.
诱导多能干细胞（iPSCs）能够生成体内的任何细胞类型，这使其成为细胞替代疗法的宝贵工具。然而，iPSCs的分化可能具有挑战性，过程缓慢且存在差异。在分化过程中，染色质会重新组织，沉默的致密异染色质会通过涉及核纤层和内核膜（INM）蛋白的过程与核周边相连。INM蛋白Samp1（纺锤体相关膜蛋白1）与核纤层蛋白A/C以及具有染色质结合LEM（Lap2-Emerin-Man1）结构域的INM蛋白Emerin相互作用。在本文中，我们研究Samp1是否能在iPSCs的分化中发挥作用。随着分化的iPSCs开始表达核纤层蛋白A/C，Samp1的水平升高。有趣的是，即使在多能培养条件下，Samp1的异位表达也会诱导iPSCs快速分化，其中一些在6天后就已经表达神经元标志物βIII-微管蛋白。这表明Samp1参与了iPSCs的早期分化，并且有可能作为促进分化过程进展的工具进行探索。
