scholarly journals LncRNA and mRNA Expression Profiles in Methylprednisolone Stimulated Neural Stem Cells

2021 ◽  
Vol 15 ◽  
Author(s):  
Yong Tang ◽  
Zhongyu Xie ◽  
Mengjun Ma ◽  
Kaidi Duan ◽  
Yuxi Li ◽  
...  

Spinal cord injury (SCI) is a devastating neurological disorder that affects thousands of individuals each year. Previously, our study in non-human primates with SCI demonstrated that methylprednisolone (MP) resulted in the dysfunction of neural stem cells (NSCs), which may help to explain the controversial roles of MP in SCI. However, the detailed mechanism is still unclear. In this manuscript, we investigated the LncRNA and mRNA expression profiles of NSCs treated with MP. A total of 63 differentially expressed LncRNAs and 174 differentially expressed mRNAs were identified. Gene ontology (GO) analysis showed that differentially expressed mRNAs were highly associated with terms related to regulation of external stimulation, secretion, and migration. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results indicated that the PI3K–Akt signaling pathway contributed to the functions of MP treated NSCs. Besides, 3899 co-expression pairs were constructed among the differentially expressed LncRNA and mRNA, among which five predicted target mRNAs with the differentially expressed LncRNAs were identified. These results provide greater insight into the precise mechanisms of MP mediating NSC dysfunction in SCI.

2020 ◽  
Vol 15 (1) ◽  
pp. 77-88 ◽  
Author(s):  
Qichang Yang ◽  
Jing Wu ◽  
Jian Zhao ◽  
Tianyi Xu ◽  
Ping Han ◽  
...  

Background: Previous studies indicated that the cell fate of neural stem cells (NSCs) after differentiation is determined by Smek1, one isoform of suppressor of Mek null (Smek). Smek deficiency prevents NSCs from differentiation, thus affects the development of nervous system. In recent years, lncRNAs have been found to participate in numerous developmental and biological pathways. However, the effects of knocking out Smek on the expression profiles of lncRNAs during the differentiation remain unknown. Objective: This study is to explore the expression profiles of lncRNAs and their possible function during the differentiation from Smek1/2 knockout NSCs. Methods: We obtained NSCs from the C57BL/6J mouse fetal cerebral cortex. One group of NSCs was from wildtype mouse (WT group), while another group was from knocked out Smek1/2 (KO group). Results: By analyzing the RNA-Seq data, we found that after knocking out Smek1/2, the expression profiles of mRNAs and lncRNAs revealed significant changes. Analyses indicated that these affected mRNAs have connections with the pathway network for the differentiation and proliferation of NSCs. Furthermore, we performed a co-expression network analysis on the differentially expressed mRNAs and lncRNAs, which helped reveal the possible regulatory rules of lncRNAs during the differentiation after knocking out Smek1/2. Conclusion: By comparing group WT with KO, we found 366 differentially expressed mRNAs and 12 lncRNAs. GO and KEGG enrichment analysis on these mRNAs suggested their relationships with differentiation and proliferation of NSCs. Some of these mRNAs and lncRNAs have been verified to play regulatory roles in nervous system. Analyses on the co-expression network also indicated the possible functions of affected mRNAs and lncRNAs during NSCs differentiation after knocking out Smek1/2.


Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 882 ◽  
Author(s):  
Amirnasr ◽  
Gits ◽  
van Kuijk ◽  
Smid ◽  
Vriends ◽  
...  

Despite the success of imatinib in advanced gastrointestinal stromal tumor (GIST) patients, 50% of the patients experience resistance within two years of treatment underscoring the need to get better insight into the mechanisms conferring imatinib resistance. Here the microRNA and mRNA expression profiles in primary (imatinib-naïve) and imatinib-resistant GIST were examined. Fifty-three GIST samples harboring primary KIT mutations (exon 9; n = 11/exon 11; n = 41/exon 17; n = 1) and comprising imatinib-naïve (IM-n) (n = 33) and imatinib-resistant (IM-r) (n = 20) tumors, were analyzed. The microRNA expression profiles were determined and from a subset (IM-n, n = 14; IM-r, n = 15) the mRNA expression profile was established. Ingenuity pathway analyses were used to unravel biochemical pathways and gene networks in IM-r GIST. Thirty-five differentially expressed miRNAs between IM-n and IM-r GIST samples were identified. Additionally, miRNAs distinguished IM-r samples with and without secondary KIT mutations. Furthermore 352 aberrantly expressed genes were found in IM-r samples. Pathway and network analyses revealed an association of differentially expressed genes with cell cycle progression and cellular proliferation, thereby implicating genes and pathways involved in imatinib resistance in GIST. Differentially expressed miRNAs and mRNAs between IM-n and IM-r GIST were identified. Bioinformatic analyses provided insight into the genes and biochemical pathways involved in imatinib-resistance and highlighted key genes that may be putative treatment targets.


Author(s):  
Baokun Sui ◽  
Dong Chen ◽  
Wei Liu ◽  
Bin Tian ◽  
Lei Lv ◽  
...  

Rabies is a lethal disease caused by Rabies lyssavirus, commonly known as rabies virus (RABV), and results in nearly 100 % death once clinical symptoms occur in human and animals. Long non-coding RNAs (lncRNAs) have been reported to be associated with viral infection. But the role of lncRNAs involved in RABV infection is still elusive. In this study, we performed global transcriptome analysis of both of lncRNA and mRNA expression profiles in wild-type (WT) and lab-attenuated RABV-infected mouse brains by using next-generation sequencing. The differentially expressed lncRNAs and mRNAs were analysed by using the edgeR package. We identified 1422 differentially expressed lncRNAs and 4475 differentially expressed mRNAs by comparing WT and lab-attenuated RABV-infected brains. Then we predicted the enriched biological pathways by the Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) database based on the differentially expressed lncRNAs and mRNAs. Our analysis revealed the relationships between lncRNAs and RABV-infection-associated immune response and ion transport-related pathways, which provide a fresh insight into the potential role of lncRNA in immune evasion and neuron injury induced by WT RABV.


2020 ◽  
pp. 1-8
Author(s):  
Sahar Kiani ◽  
Atiyeh Mohammadshirazi ◽  
Maedeh Kashkouli ◽  
Ebrahim Shahbazi ◽  
Hassan Asghari ◽  
...  

Background: Traumatic injury to the spinal cord causes cell death, demyelination, axonal degeneration, and cavitation, resulting in functional motor and sensory loss. Stem cell therapy as a promising approach for spinal cord injury (SCI) has some challenges, such as immunological responses to grafted cells. Transplantation of autologous trans-differentiated cells can be a useful strategy to overcome this problem. Materials and Methods: In this research, we transplanted human-induced neural stem cells (hiNSCs), which were trans-differentiated from adult human fibroblasts into the injured spinal cord of adult rats on day seven post-injury. Before transplantation, hiNSCs were explored for expressing NSCs general protein and genes and also, their normal karyotype was examined. After hiNSCs transplantation, behavioural tests (BBB score and grid walk tests) were performed weekly and finally histological assessment was done for exploring the cell fates and migration. Results: Our results showed the cell viability, differentiation, and migration of transplanted hiNSCs was significantly improved in the injured site of the spinal cord up to seven weeks after the SCI. Also, the behavioural analysis revealed the enhanced locomotor functions of the animals that underwent transplantation after seven weeks. Our data provide strong evidence in support of the feasibility of hiNSCs for cell-based therapy in SCI rats.


2021 ◽  
Vol 22 (8) ◽  
pp. 3913
Author(s):  
Satoshi Nakata ◽  
Ming Yuan ◽  
Jeffrey A. Rubens ◽  
Ulf D. Kahlert ◽  
Jarek Maciaczyk ◽  
...  

Central nervous system tumor with BCL6-corepressor internal tandem duplication (CNS-BCOR ITD) is a malignant entity characterized by recurrent alterations in exon 15 encoding the essential binding domain for the polycomb repressive complex (PRC). In contrast to deletion or truncating mutations seen in other tumors, BCOR expression is upregulated in CNS-BCOR ITD, and a distinct oncogenic mechanism has been suggested. However, the effects of this change on the biology of neuroepithelial cells is poorly understood. In this study, we introduced either wildtype BCOR or BCOR-ITD into human and murine neural stem cells and analyzed them with quantitative RT-PCR and RNA-sequencing, as well as growth, clonogenicity, and invasion assays. In human cells, BCOR-ITD promoted derepression of PRC2-target genes compared to wildtype BCOR. A similar effect was found in clinical specimens from previous studies. However, no growth advantage was seen in the human neural stem cells expressing BCOR-ITD, and long-term models could not be established. In the murine cells, both wildtype BCOR and BCOR-ITD overexpression affected cellular differentiation and histone methylation, but only BCOR-ITD increased cellular growth, invasion, and migration. BCOR-ITD overexpression drives transcriptional changes, possibly due to altered PRC function, and contributes to the oncogenic transformation of neural precursors.


2021 ◽  
Vol 22 (9) ◽  
pp. 4604
Author(s):  
Giuliana Mannino ◽  
Anna Longo ◽  
Florinda Gennuso ◽  
Carmelina Daniela Anfuso ◽  
Gabriella Lupo ◽  
...  

A pericyte-like differentiation of human adipose-derived mesenchymal stem cells (ASCs) was tested in in vitro experiments for possible therapeutic applications in cases of diabetic retinopathy (DR) to replace irreversibly lost pericytes. For this purpose, pericyte-like ASCs were obtained after their growth in a specific pericyte medium. They were then cultured in high glucose conditions to mimic the altered microenvironment of a diabetic eye. Several parameters were monitored, especially those particularly affected by disease progression: cell proliferation, viability and migration ability; reactive oxygen species (ROS) production; inflammation-related cytokines and angiogenic factors. Overall, encouraging results were obtained. In fact, even after glucose addition, ASCs pre-cultured in the pericyte medium (pmASCs) showed high proliferation rate, viability and migration ability. A considerable increase in mRNA expression levels of the anti-inflammatory cytokines transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) was observed, associated with reduction in ROS production, and mRNA expression of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), and angiogenic factors. Finally, a pmASC-induced better organization of tube-like formation by retinal endothelial cells was observed in three-dimensional co-culture. The pericyte-like ASCs obtained in these experiments represent a valuable tool for the treatment of retinal damages occurring in diabetic patients.


Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 506
Author(s):  
Xiaolong Wang ◽  
Yongliang Fan ◽  
Yifan He ◽  
Ziyin Han ◽  
Zaicheng Gong ◽  
...  

Staphylococcus aureus- induced mastitis is one of the most intractable problems for the dairy industry, which causes loss of milk yield and early slaughter of cows worldwide. Few studies have used a comprehensive approach based on the integrative analysis of miRNA and mRNA expression profiles to explore molecular mechanism in bovine mastitis caused by S. aureus. In this study, S. aureus (A1, B1 and C1) and sterile phosphate buffered saline (PBS) (A2, B2 and C2) were introduced to different udder quarters of three individual cows, and transcriptome sequencing and microarrays were utilized to detected miRNA and gene expression in mammary glands from the challenged and control groups. A total of 77 differentially expressed microRNAs (DE miRNAs) and 1625 differentially expressed genes (DEGs) were identified. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that multiple DEGs were enriched in significant terms and pathways associated with immunity and inflammation. Integrative analysis between DE miRNAs and DEGs proved that miR-664b, miR-23b-3p, miR-331-5p, miR-19b and miR-2431-3p were potential factors regulating the expression levels of CD14 Molecule (CD14), G protein subunit gamma 2 (GNG2), interleukin 17A (IL17A), collagen type IV alpha 1 chain (COL4A1), microtubule associated protein RP/EB family member 2 (MAPRE2), member of RAS oncogene family (RAP1B), LDOC1 regulator of NFKB signaling (LDOC1), low-density lipoprotein receptor (LDLR) and S100 calcium binding protein A9 (S100A9) in bovine mastitis caused by S. aureus. These findings could enhance the understanding of the underlying immune response in bovine mammary glands against S. aureus infection and provide a useful foundation for future application of the miRNA–mRNA-based genetic regulatory network in the breeding cows resistant to S. aureus.


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