Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd #2900A, Los Angeles, CA, 90048, USA.
Gecorp, Av Juan Manuel de Rosas 899, San Miguel del Monte, Buenos Aires, Argentina.
Sci Rep. 2023 Jul 22;13(1):11829. doi: 10.1038/s41598-023-38671-z.
Newts have the extraordinary ability to fully regenerate lost or damaged cardiac, neural and retinal tissues, and even amputated limbs. In contrast, mammals lack these broad regenerative capabilities. While the molecular basis of newts' regenerative ability is the subject of active study, the underlying paracrine signaling factors involved remain largely uncharacterized. Extracellular vesicles (EVs) play an important role in cell-to-cell communication via EV cargo-mediated regulation of gene expression patterns within the recipient cells. Here, we report that newt myogenic precursor (A1) cells secrete EVs (A1EVs) that contain messenger RNAs associated with early embryonic development, neuronal differentiation, and cell survival. Exposure of rat primary superior cervical ganglion (SCG) neurons to A1EVs increased neurite outgrowth, facilitated by increases in mitochondrial respiration. Canonical pathway analysis pinpointed activation of NGF/ERK5 signaling in SCG neurons exposed to A1EV, which was validated experimentally. Thus, newt EVs drive neurite growth and complexity in mammalian primary neurons.
蝾螈具有完全再生丢失或受损的心脏、神经和视网膜组织，甚至断肢的非凡能力。相比之下，哺乳动物缺乏这些广泛的再生能力。虽然蝾螈再生能力的分子基础是活跃的研究课题，但涉及的潜在旁分泌信号因子在很大程度上仍未被描述。细胞外囊泡 (EVs) 通过 EV 货物介导的受体内基因表达模式的调节，在细胞间通讯中发挥重要作用。在这里，我们报告说，蝾螈成肌前体细胞 (A1) 细胞分泌含有与早期胚胎发育、神经元分化和细胞存活相关的信使 RNA 的 EV (A1EV)。将 A1EV 暴露于大鼠原代颈上神经节 (SCG) 神经元可增加神经突生长，这是通过增加线粒体呼吸来实现的。经典途径分析确定了 A1EV 暴露的 SCG 神经元中 NGF/ERK5 信号的激活，这在实验上得到了验证。因此，蝾螈 EV 驱动哺乳动物原代神经元的神经突生长和复杂性。
