Molecular Signatures of Regenerating Blastema Cells -Analysis of gene expression patterns in regenerating newt limbs compared to human/murine stem cells to learn to equip induced pluripotent stem cells with regenerative capacities.

火蜥蜴的肢体再生是一个令人着迷的现象，被截肢的肢体不仅被正确地替换，而且正确的空间模式也被重建。在截肢部位，细胞去分化，形成来自所有受影响组织的细胞混合物，称为胚泡。这一建议包括通过转录组分析和检测其在体外和体内的分化潜力，通过植入研究，建立分离的胚泡细胞的分子特征，因为胚芽细胞在肢体再生过程中重建肌肉骨骼结构。分离的胚泡细胞的分化潜力将与已知的人类和小鼠干细胞的特征进行比较。有一种假说认为，蝾螈使用一组与哺乳动物不同的新基因来对损伤和截肢做出强有力的再生反应，因此人们有望识别出一种新的基因表达模式。这将为以下问题提供独特的见解：为什么火蜥蜴能够再生身体的任何部位，而老鼠或人类则不能。这些数据将使未来对已识别的分子特征的表观遗传修饰的研究成为可能，并将指导重新编程小鼠和人类干细胞的努力，目标是使它们具有新的再生能力。

Limb regeneration in salamanders is a fascinating phenomenon where amputated extremities are not only replaced properly, but the correct spatial pattern is rebuilt as well. At the amputation site cells dedifferentiate to form a mixture of cells derived from all affected tissues called blastema. This proposal comprises the establishment of the molecular signature of isolated blastema cells by transcriptome analysis and examination of their differentiation potential in vitro and in vivo, by implantation studies, as blastema cells rebuild musculoskeletal structures during limb regeneration. The differentiation potential of isolated blastema cells will be compared with known signatures of human and mouse stem cells. Having the hypothesis that newts use a novel set of genes, distinct from those in mammalians to mount a robust regenerative response to injury and amputation, the identification of a new gene expression pattern is expected. This will provide unique insights into the question why salamanders are able to regenerate any body part, while mice or humans cannot. These data will enable future studies on epigenetic modifications for identified molecular signatures and will also guide efforts to reprogram mouse and human stem cells with the goal to equip them with novel regenerative capacities.