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.

蝾螈的肢体再生是一个令人着迷的现象，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，称为胚质。本提案包括通过转录组分析建立分离囊胚细胞的分子特征，并通过植入研究检查其体外和体内分化潜力，因为囊胚细胞在肢体再生过程中重建肌肉骨骼结构。分离的囊胚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。假设蝾螈使用一组不同于哺乳动物的新基因对损伤和截肢产生强大的再生反应，那么鉴定一种新的基因表达模式是有希望的。这将为“为什么蝾螈能够再生身体的任何部位，而老鼠或人类却不能”这个问题提供独特的见解。这些数据将使未来的表观遗传修饰研究能够识别分子特征，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.