Messa Letizia, Barzaghini Bianca, Rey Federica, Pandini Cecilia, Zuccotti Gian Vincenzo, Cereda Cristina, Carelli Stephana, Raimondi Manuela Teresa
Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, 20157 Milan, Italy.
Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Via Grassi 74, 20157 Milan, Italy.
Biomedicines. 2021 Aug 31;9(9):1120. doi: 10.3390/biomedicines9091120.
Non-coding RNAs show relevant implications in various biological and pathological processes. Thus, understanding the biological implications of these molecules in stem cell biology still represents a major challenge. The aim of this work is to study the transcriptional dysregulation of 357 non-coding genes, found through RNA-Seq approach, in murine neural precursor cells expanded inside the 3D micro-scaffold Nichoid versus standard culture conditions. Through weighted co-expression network analysis and functional enrichment, we highlight the role of non-coding RNAs in altering the expression of coding genes involved in mechanotransduction, stemness, and neural differentiation. Moreover, as non-coding RNAs are poorly conserved between species, we focus on those with human homologue sequences, performing further computational characterization. Lastly, we looked for isoform switching as possible mechanism in altering coding and non-coding gene expression. Our results provide a comprehensive dissection of the 3D scaffold Nichoid's influence on the biological and genetic response of neural precursor cells. These findings shed light on the possible role of non-coding RNAs in 3D cell growth, indicating that also non-coding RNAs are implicated in cellular response to mechanical stimuli.
非编码RNA在各种生物学和病理过程中显示出相关影响。因此，了解这些分子在干细胞生物学中的生物学意义仍然是一项重大挑战。这项工作的目的是研究通过RNA测序方法在三维微支架Nichoid中与标准培养条件下扩增的小鼠神经前体细胞中发现的357个非编码基因的转录失调。通过加权共表达网络分析和功能富集，我们突出了非编码RNA在改变参与机械转导、干性和神经分化的编码基因表达中的作用。此外，由于非编码RNA在物种间保守性较差，我们聚焦于具有人类同源序列的非编码RNA，进行进一步的计算表征。最后，我们寻找异构体切换作为改变编码和非编码基因表达的可能机制。我们的结果全面剖析了三维支架Nichoid对神经前体细胞生物学和遗传反应的影响。这些发现揭示了非编码RNA在三维细胞生长中的可能作用，表明非编码RNA也参与细胞对机械刺激的反应。
