## 3 Results
### Role of lncRNAs: Focus on Sequence Conservation and Relevance of Human Homologues
A detailed description of lncRNAs with human homologue, as well as the MFE minimization energy predicted is reported in Table 3.  
Deregulated LncRNAs Result Associated with Stem Cells Features: Mechanotransduction, Stemness, and Neuronal Differentiation  
As already demonstrated, NPCs' growth inside the Nichoid present altered expression of genes that regulate mechanotransduction and stem cells fate [30; 32]. Moreover, as there is a specific alteration of the lncRNAs expression as result of cells' expansion inside the Nichoid, we investigated whether this could be due to mechanotransduction or stemness-TF regulation. Thus, we predicted the presence of transcription factors binding sites for lncRNAs with human homologue across regulatory region of interest such as promoters or enhancers through the AnnoLnc2 database and the Ciiider software [71], which highlighted 644 TFs. Specifically, among them, 30 out of 644 were associated with mechanotransduction (Figure 6A), 8 with stemness TFs (Figure 6B), and 20 with neural lineage TFs (Figure 6C) [72; 73]. When considering TFs related to mechanotransduction, we identified 12 out of 30 TFs involved in cell proliferation, differentiation, and morphogenesis (_KLF4_, _HOXA5_, _ATF1_, _BF2_, _BF3_, _EGR1_, _ETS1_, _FOS_, _HOXA_, _KLF5_, _OTX1_, _OTX2_) as shown \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Gene Name** & **log2 FC** & **MFE Minimization** & **Description** \\ \hline _Miat_ & 2.22 & \(-3699\) kcal/mol & This gene encodes a spliced long non-coding RNA that may constitute a component of the nuclear matrix. Altered expression of a similar gene in human has been associated with a susceptibility to myocardial infarction, and is involved in pathways that may contribute to the pathophysiology of schizophrenia. \\ _Linc-pint_ & 1.89 & \(-559.80\) kcal/mol & lncRNA, Trp53 induced transcript. Its inhibition affects insulin secretion and apoptosis in mouse pancreatic \(\beta\) cells [69]. \\ _Mir17 hg_ & 1.77 & \(-1046.20\) kcal/mol & Angiogenesis. Amplification of this gene has been found in several lymphomas and solid tumors \\ _Mir670 hg_ & 1.74 & \(-313.30\) kcal/mol & RNA Gene affiliated with the lncRNA class. No more information are given \\ _C130071C03 Rik_ & \(-1.12\) & \(-997.50\) kcal/mol & It facilitates neutralization by inhibiting miR-101a-3p’s ability to reduce GSK-3\(\beta\) level [67] \\ _Trp53 cor1_ & \(-1.34\) & \(-1075.40\) kcal/mol & tumor protein p53 pathway corepressor 1, which is involved also in Parkinson Disease and stemness maintenance [70] \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Summary of lncRNAs with a human homologue. Columns report gene name, log2 FC, MFE minimization according to the secondary structure prediction and description. Descriptions were taken from literature andncbi gene bank ([[https://www.ncbi.nlm.nih.gov/gene/](https://www.ncbi.nlm.nih.gov/gene/)]([https://www.ncbi.nlm.nih.gov/gene/](https://www.ncbi.nlm.nih.gov/gene/)) (accessed on 25 February 2021)). in Figure 6A [74]. _OTX1_ and _OTX2_ activate genes whose encoded proteins influence the proliferation and differentiation of dopaminergic neuronal progenitor cells during mitosis. Interestingly, among the mechanotransduction-related TFs _EBF2_, _ETS1_, _FOS RINX2_, _SOX9_, and _STAT3_ were predicted also as TFs binding sites for all lncRNAs of interest in the AnnoLnc2 database. Moreover, _FoS1_, _Fos2_, and _Klf5_ were found upregulated in transcriptomic analysis, suggesting that, along with lncRNAs, they could all be part of a common regulatory network that affects proliferation and morphology. Given the importance of the Nichoid in promoting proliferation and stemness potential, we focused our attention also on possible TFs binding sites related to stemness as reported in Figure 6B. In particular, _Myc, Sox2_, _Oct4_, and _Smad3_, key regulators of pluripotency, emerged also as TFs for these lncRNAs both through the Ciiider software and the AnnoLnc2 database, suggesting that their binding could regulate gene expression with relevance for stemness maintenance.