4.7 Article

Neural Precursor Cells Expanded Inside the 3D Micro-Scaffold Nichoid Present Different Non-Coding RNAs Profiles and Transcript Isoforms Expression: Possible Epigenetic Modulation by 3D Growth

Journal

BIOMEDICINES
Volume 9, Issue 9, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines9091120

Keywords

Nichoid; RNA-seq; non-coding RNAs; RNA interactions; mechanotransduction; 3D-microscaffold; alternative splicing; isoform switching

Funding

  1. European Research Council (ERC) [646990, 754467, 825159]
  2. European Commission [964481]
  3. European Space Agency (ESA) [4000133244/20/NL/GLC]
  4. National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [NC/C01903/1, NC/C019201/1]
  5. Italian Ministry of University and Research (MIUR-FARE project BEYOND) [R16ZNN2R9K]
  6. Fondazione Social Venture Giordano Dell'Amore
  7. Cariplo Factory
  8. Politecnico di Milano
  9. Fondazione Bassetti
  10. Fondazione Triulza
  11. Pediatric Clinical Research Center Fondazione Romeo and Enrica Invernizzi
  12. European Research Council (ERC) [754467, 825159] Funding Source: European Research Council (ERC)

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This study investigated the transcriptional dysregulation of 357 non-coding genes in murine neural precursor cells and highlighted their role in altering the expression of coding genes involved in mechanotransduction, stemness, and neural differentiation. Furthermore, computational characterization of non-coding RNAs with human homologue sequences was performed to explore their mechanisms of action.
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.

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