Dissecting the Effect of a 3D Microscaffold on the Transcriptome of Neural Stem Cells with Computational Approaches: A Focus on Mechanotransduction.
3D cell cultures are becoming more and more important in the field of regenerative medicine due to their ability to mimic the cellular physiological microenvironment. Among the different types of 3D scaffolds, we focus on the Nichoid, a miniaturized scaffold with a structure inspired by the natural staminal niche. The Nichoid can activate cellular responses simply by subjecting the cells to mechanical stimuli. This kind of influence results in different cellular morphology and organization, but the molecular bases of these changes remain largely unknown. Through RNA-Seq approach on murine neural precursors stem cells expanded inside the Nichoid, we investigated the deregulated genes and pathways showing that the Nichoid causes alteration in genes strongly connected to mechanobiological functions. Moreover, we fully dissected this mechanism highlighting how the changes start at a membrane level, with subsequent alterations in the cytoskeleton, signaling pathways, and metabolism, all leading to a final alteration in gene expression. The results shown here demonstrate that the Nichoid influences the biological and genetic response of stem cells thorough specific alterations of cellular signaling. The characterization of these pathways elucidates the role of mechanical manipulation on stem cells, with possible implications in regenerative medicine applications.
['Rey|Federica|F|0000-0001-7944-3143', 'Pandini|Cecilia|C|', 'Barzaghini|Bianca|B|', 'Messa|Letizia|L|', 'Giallongo|Toniella|T|', 'Pansarasa|Orietta|O|0000-0002-3041-0612', 'Gagliardi|Stella|S|0000-0002-6589-6907', 'Brilli|Matteo|M|0000-0001-9891-4617', 'Zuccotti|Gian Vincenzo|GV|0000-0002-2795-9874', 'Cereda|Cristina|C|', 'Raimondi|Manuela Teresa|MT|0000-0003-2585-7206', 'Carelli|Stephana|S|0000-0003-4603-396X']
D000818:Animals D018929:Cell Culture Techniques D002478:Cells, Cultured D003599:Cytoskeleton D015870:Gene Expression D040542:Mechanotransduction, Cellular D051379:Mice D008810:Mice, Inbred C57BL D058953:Neural Stem Cells D044968:Regenerative Medicine D015398:Signal Transduction D055153:Stem Cell Niche D054457:Tissue Scaffolds D059467:Transcriptome
neural stem cells mechanotransduction regenerative medicine scaffolds niche RNA-Seq mechanobiology computational genomics signal transduction