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Cardiovascular progenitor cells cultured aboard the International Space Station exhibit altered developmental and functional properties
npj Microgravity ( IF 5.1 ) Pub Date : 2018-07-26 , DOI: 10.1038/s41526-018-0048-x
Jonathan Baio , Aida F. Martinez , Ivan Silva , Carla V. Hoehn , Stephanie Countryman , Leonard Bailey , Nahidh Hasaniya , Michael J. Pecaut , Mary Kearns-Jonker

The heart and its cellular components are profoundly altered by missions to space and injury on Earth. Further research, however, is needed to characterize and address the molecular substrates of such changes. For this reason, neonatal and adult human cardiovascular progenitor cells (CPCs) were cultured aboard the International Space Station. Upon return to Earth, we measured changes in the expression of microRNAs and of genes related to mechanotransduction, cardiogenesis, cell cycling, DNA repair, and paracrine signaling. We additionally assessed endothelial-like tube formation, cell cycling, and migratory capacity of CPCs. Changes in microRNA expression were predicted to target extracellular matrix interactions and Hippo signaling in both neonatal and adult CPCs. Genes related to mechanotransduction (YAP1, RHOA) were downregulated, while the expression of cytoskeletal genes (VIM, NES, DES, LMNB2, LMNA), non-canonical Wnt ligands (WNT5A, WNT9A), and Wnt/calcium signaling molecules (PLCG1, PRKCA) was significantly elevated in neonatal CPCs. Increased mesendodermal gene expression along with decreased expression of mesodermal derivative markers (TNNT2, VWF, and RUNX2), reduced readiness to form endothelial-like tubes, and elevated expression of Bmp and Tbx genes, were observed in neonatal CPCs. Both neonatal and adult CPCs exhibited increased expression of DNA repair genes and paracrine factors, which was supported by enhanced migration. While spaceflight affects cytoskeletal organization and migration in neonatal and adult CPCs, only neonatal CPCs experienced increased expression of early developmental markers and an enhanced proliferative potential. Efforts to recapitulate the effects of spaceflight on Earth by regulating processes described herein may be a promising avenue for cardiac repair.



中文翻译:

在国际空间站上培养的心血管祖细胞显示出改变的发育和功能特性

心脏及其细胞成分因对太空和地球伤害的使命而发生了深刻的变化。然而,需要进一步的研究来表征和解决这种变化的分子底物。因此,在国际空间站上培养了新生儿和成年人类心血管祖细胞(CPC)。回到地球后,我们测量了microRNA和与机械转导,心脏发生,细胞周期,DNA修复和旁分泌信号传导相关的基因的表达变化。我们还评估了内皮样管的形成,细胞周期和CPC的迁移能力。预测microRNA表达的变化将靶向新生儿和成人CPC中的细胞外基质相互作用和Hippo信号传导。机械转导相关基因(YAP1,RHOA)的表达下调,而新生儿CPC中的细胞骨架基因(VIMNESDESLMNB2LMNA),非经典Wnt配体(WNT5AWNT9A)和Wnt /钙信号分子(PLCG1PRKCA)的表达明显升高。中胚层基因表达增加,中胚衍生标记(TNNT2VWFRUNX2表达下降)),在新生儿CPC中观察到形成内皮样管的准备降低,并且Bmp和Tbx基因的表达升高。新生儿和成人CPC均显示出DNA修复基因和旁分泌因子表达的增加,这受到迁移增强的支持。虽然太空飞行会影响新生儿和成人CPC的细胞骨架组织和迁移,但只有新生儿CPC会经历早期发育标志物表达的增加和增殖潜能的增强。通过调节本文所述的过程来概括太空飞行对地球的影响的努力可能是心脏修复的有前途的途径。

更新日期:2019-11-18
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