Research ArticleExperimental Studies
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Induction of Targeted Differentiation of Dermal Mesenchymal Stem Cells Into Neural Lineage According to Peroxiredoxin II Expression

YING-HAO HAN, XIAO-YA XING, DONG HUN LEE, YING-YING MAO, MEI-HUA JIN, HU-NAN SUN and TAEHO KWON
In Vivo July 2023, 37 (4) 1593-1602; DOI: https://doi.org/10.21873/invivo.13244

Abstract

Background/Aim: To optimize the therapeutic potential of stem cells in stem cell therapy for neurological diseases, it is crucial to enhance the differentiation, migration, and neural network formation of stem cells, and to eliminate uncertain cell differentiation and proliferation factors. Several studies have shown that reactive oxygen species (ROS) are important factors in the regulation of neurogenesis, and Prx II (Peroxiredoxin II) is a gene that regulates ROS. Materials and Methods: As the entry point in this study to conduct a bioinformatics analysis of the sequencing results of Prx II+/+ dermal mesenchymal stem cells (DMSCs) and Prx II−/− DMSCs. lncRNA/miRNA/mRNA networks were then constructed and preliminarily verified in RT-qPCR experiments. Results: In this study, a total of 11 hub genes (Gria1, Nrcam, Sox10, Snap25, Cntn2, Dlg2, Ngf, Ntrk3, Amph, Syt1, and Cd24a), eight miRNAs (miRNA-4661, miRNA-34a, miRNA-185, miRNA-34b-5p, miRNA-34c, miRNA-449a, miRNA-449b, miRNA-449c) and 12 lncRNAs (Dubr, Gas5, Gm20427, Gm26917, Gm42547, Gm8066, Kcnq1ot1, Malat1, Mir17hg, Neat1, Rian, and Tug1) were predicted in lncRNA/miRNA/mRNA network. Conclusion: The regulatory mechanism of Prx II in the differentiation of DMSCs into neurons through ROS was explored, and a theoretical basis was determined that can be applied in future research on nervous system diseases and the clinical applications of stem cells.

Key Words:

The development of new and more effective protocols for treating neurological diseases is urgently needed (1). Regenerative medicine based on stem cell therapy provides new breakthroughs for treating neurological diseases by replacing damaged or lost cells with stem cells that have the differentiation ability to repair damaged neuronal tissues (2). Many studies have shown that mesenchymal stem cells (MSCs) have the ability to secrete neurotrophic and proangiogenesis factors (3), be immunomodulatory (4), undergo tissue remodeling to maintain the blood-brain barrier (5), activate progenitor cells to differentiate into neurons (6), and self-differentiate into neurons (7).

Peroxiredoxins (Prxs) play an important role in the regulation of oxidative stress-induced signaling pathways. A growing number of studies have demonstrated the role of Prxs in maintaining stem cells, and studies have suggested that Prx II knockout in embryonic stem cells further increases the levels of reactive oxygen species (ROS) and accelerates their differentiation into neurons (8). However, the mechanism by which Prx II regulates the differentiation of MSCs into neurons remains unclear and requires further exploration.

In this study, the RNA sequencing results of wild-type and Prx II knockout dermal mesenchymal stem cells (Prx II+/+ DMSCs and Prx II−/− DMSCs) were bioinformatically analyzed to elucidate the mechanism by which Prx II regulates the differentiation of DMSCs to neurons through lncRNA/miRNA/mRNA. The results provide a theoretical basis for improving the differentiation efficiency of DMSCs into neurons to promote neural function recovery, and delay the progression of neurological diseases.

Materials and Methods

RNA sequencing data acquisition and processing. Illumina HiSeq 2000 was used for RNA sequencing of Prx II+/+ DMSCs and Prx II−/− DMSCs, and DESeq2 was used to compare the two groups and obtain a significant p-value and a fold-change between the genes. Based on values of p<0.05 and a fold change greater or less than 1.2 times, 472 differentially expressed genes (DEGs) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the DEGs were performed.

Functional enrichment analysis of DEGs using ClueGO. In order to show the GO enrichment results more directly, ClueGO was used to show the network diagram (9), the ClueGO and CluePedia plugins of Cytoscape v.3.2.8 software were used to conduct a functional enrichment analysis of DEGs in selected biological processes (BPs) using p<0.05 as the threshold.

Construction of protein-protein interaction (PPI) network for DEGs. To determine the interactions between DEGs, up-regulated DEGs enriched in three GO-BP classes, including neuronal differentiation and development, axonal dendritic development transmission, and neurotrophic factor secretion, were analyzed using the STRING database (10), with a default confidence level of ≥0.4.

Hub genes obtained through the Cytoscape Network Analytics tool. The PPI network was visualized using Cytoscape v. 3.2.8 software and computed using a Network Analytics tool based on the Betweenness Centrality (BC) and Degree parameters (11). In this experiment, DEGs with BC >0.05 and a higher than the Average Degree (AD) of each network were considered to be hub genes.

Prediction and construction of LncRNA/miRNA/mRNA interaction networks. A lncRNA/miRNA/mRNA interaction network was constructed by combining the results from the miRWalk and StarBase databases (12). Five databases were selected for cross-validation using miRWalk, and miRNAs from three or more databases were retained. To improve the confidence and accuracy of the prediction, it was only possible to predict upstream lncRNAs using the StarBase database if three or more hub genes were simultaneously targeted. All data were processed and presented using the Cytoscape software.

Use of reverse transcription-qPCR to verify results. Skin samples from mice were digested in 0.25% trypsin-EDTA to separate the dermis from the epidermal layer. Mouse DMSCs were then extracted by digestion with 0.25% trypsin-EDTA for about 1 h and seeded in DMEM/F12 medium. Total RNA was extracted using a UNlQ-10 Column Total RNA Purification Kit (Sangon, Shanghai, PR China). RT-PCR was run using 2×Taq SYBRGreen qPCR PreMix (Innovagene, Hunan, PR China) on a CFX96 real-time PCR system (Bio-Rad, Hercules, CA, USA). Primers were synthesized and designed by Sangon based on the gene sequences (Table I and Table II). Hub gene, miRNA, and lncRNA fold changes were quantified using the 2−ΔΔCq method.

View this table:
Table I.

mRNA and lncRNA primer sequences.

View this table:
Table II.

miRNA primer sequences.

Statistical analysis. Statistical analyses were performed using IBM SPSS Statistics Version 25 (IBMCorp., Armonk, NY, USA). Continuous variables are expressed as means±SD. Statistical significance was set at p<0.05.

Results

DEG enrichment analyses. The KEGG and GO enrichment analyses of the DEGs showed that the up-regulated KEGG enrichment set was significantly enriched in the neurotrophin signaling pathway (Figure 1A), and most of the GO-enriched entries were also related to neurons (Figure 1B). Therefore, we hypothesized that Prx II plays an important role in the regulation of neuronal differentiation. To explore the mechanism by which Prx II regulates the differentiation of DMSCs into neurons, the neurotrophin signaling pathway can be used through neuronal differentiation and development, axonal dendritic development, and secretion of neurotrophic factors. We therefore classified items that were significantly enriched in GO-BPs (Figure 2A), and ClueGo and CluePedia Cytoscape plugins were employed to visualize the GO-BP interaction network (Figure 2B, C, and D). According to the GO and KEGG enrichment results of DEGs, Prx II plays a potential regulatory role in the differentiation of DMSCs into neurons.

Figure 1.
Figure 1.

Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. (A) GO enrichment terms for up-regulated genes between Prx II−/− and Prx II+/+ dermal mesenchymal stem cells (DMSCs). (B) KEGG enrichment terms for up-regulated genes between Prx II−/− and Prx II+/+ DMSCs.

Figure 2.
Figure 2.

Differentially expressed genes enrichment analysis. (A) Gene ontology (GO) enrichment terms for up-regulated genes between Prx II−/− and Prx II+/+ dermal mesenchymal stem cells (DMSCs) in axon dendrite developmental transmission, neuronal differentiation and development, neurotrophic factor secretion; (B, C, D) analysis of GO-BP interaction networks using ClueGO.

PPI analysis of DEGs. A PPI analysis of DEGs involved in neuronal differentiation and development, axonal dendritic development, transmission, and neurotrophic factor secretion was performed using the Retrieval of Interacting Genes (STRING) tool, and the results were visualized using the network visualization tool Cytoscape (Figure 3A, B, and C). The node colors from green to blue represent BC values from high to low, and the node size indicates the magnitude of the degree value. The degree indicates the number of interactions of a particular protein. The hub genes were identified using Network Analytics (Table III). Eleven hub genes were identified, including Griya1, Nrcam, Sox10, Snap25, Cntn2, Dlg2, Ngf, Ntrk3, Amph, Syt1, and Cd24a. Gene expression was verified using RT-qPCR (Figure 3D). As key points in the network diagram, these hub genes may play key roles in Prx II-mediated regulation of DMSCs differentiation into neurons.

Figure 3.
Figure 3.

Protein-protein interaction (PPI) analysis of differentially expressed genes. (A, B, C) Visualization of PPI using Cytoscape. Node color: shades of blue to cyan color depict nodes with highest to lowest values of betweenness centrality (BC); Node size: sizes from biggest to smallest circle represent node degrees. Larger and dark colored nodes represent genes with greater numbers of links. (D) RT-qPCR was used to determine the expression of hub genes.

View this table:
Table III.

Hub gene statistics.

Prediction and analysis of upstream miRNAs of hub genes. Studies have shown that miRNAs can bind to mRNAs and regulate their degradation. Therefore, the miRNAs targeting the 11 hub genes were predicted using the miRWalk database, and the miRNAs were visualized using Cytoscape software after screening (Figure 4A). In the Figure, hub genes are represented by a purple node, miRNAs targeting one hub gene, two hub genes, three hub genes, and most hub genes are represented by a green node, dark green node, blue node, and red node, respectively. Statistically (Figure 4B), eight miRNAs were found capable of simultaneously regulating three or more pivotal genes. These eight miRNAs were miRNA-466l, miRNA-34a, miRNA-185, miRNA-34b-5p, miRNA-34c, miRNA-449a, miRNA-449b, and miRNA-449c; their expression was verified using RT-qPCR (Figure 4C), and they became the focus of subsequent analyses.

Figure 4.
Figure 4.

Prediction and analysis of upstream miRNAs of hub genes. (A) Target miRNA visualization of hub genes. Interaction network between genes involved in axon dendrite developmental transmission, neuronal differentiation and development, neurotrophic factor secretion, and their targeted miRNAs. (B) Statistical table of genes targeted by miRNA. (C) RT-qPCR was used to determine the expression of miRNA.

Upstream lncRNA prediction of miRNA. The StarBase database was used to predict the upstream lncRNAs of the miRNAs. The threshold was selected as High Severity ≥3. A visual analysis revealed that the two key lncRNAs were Gm8066 and Tug1 (Figure 5A). lncRNAs predicted for 12 miRNAs included Gm8066, Tug1, Dubr, Gas5, Gm20427, Gm26917, Gm42547, Kcnq1ot1, Malat1, Mir17hg, Neat1 and Rian. Gas5, Rian, and Tug1 were confirmed using RT-qPCR (Figure 5B). However, the lncRNA/miRNA/mRNA network of Prx II that regulates DMSC differentiation into neurons requires further study and verification.

Figure 5.
Figure 5.

LncRNA prediction upstream of miRNA. Visualization of miRNAs and upstream lncRNAs. (B) RT-qPCR was performed to determine the lncRNA expression.

Discussion

Compared to the other types of stem cells, MSCs are the most widely used in the field of regenerative medicine because they can be injected intravenously, they penetrate the blood-brain barrier, are immunosuppressive, and the ethical issues associated with their use are limited (13). However, the clinical application of primary MSCs is restricted due to their limited proliferation capacity, the gradual loss of their differentiation potential after in vitro amplification, and differences between donors (14). Prxs are highly efficient hydrogen peroxide elimination enzymes that are relatively abundant in cells compared to glutathione peroxidase and catalase, and they are the primary sensors of hydrogen peroxide signaling in most cells (15). Previous studies have shown that Prxs regulate motor neuron differentiation in the spinal cord by controlling the localization and function of glycerol phosphodiesterase 2 (GDE2) (16, 17). In embryonic stem cells (ESCs), Prxs control the process of neuronal differentiation; during neuronal differentiation, ROS and Prx II levels are elevated and Prx I levels are decreased. Knocking down Prx II in ESCs further increases ROS levels, and downstream ROS-sensitive signals are activated to accelerate ESC differentiation into neurons; when N-Acetylcysteine (NAC) inhibitors are used, the activated ROS-sensitive signals are inhibited, and neuronal differentiation is inhibited (8). Recent studies have shown that Prx VI can induce the differentiation of bone marrow MSCs into neurons cultured in vitro (18). The redox state of a cell determines its fate by controlling the functions of different proteins during differentiation. These studies suggest that once the differentiation process begins, Prx II controls neuronal differentiation by regulating ROS levels. Preliminary laboratory studies have shown that Prx II-deficient DMSCs have a more pronounced effect on trauma treatment by increasing exosome secretion, which suggests the potential advantages of using Prx II−/− DMSCs to treat diseases. RNA sequencing results for Prx II+/+ DMSCs and Prx II−/− DMSCs have shown that Prx II−/− DMSCs are less immunogenic, which reduces the risks of stem cell therapy (19). In this study, we compared RNA sequencing results from Prx II+/+ DMSCs and Prx II−/− DMSCs. A total of 472 DEGs were identified, of which 176 and 296 were up-regulated and down-regulated, respectively. A differential gene enrichment analysis revealed that Prx II regulates the differentiation of DMSCs into neurons.

It has become widely accepted in recent years that lncRNAs play key roles in various biological processes. In addition, growing experimental evidence supports the role of lncRNAs as competing endogenous RNA (ceRNAs) that compete with miRNAs, thereby up-regulating mRNA expression (20). The expression level of Gas5, Rian, and Tug1 lncRNAs predicted in this study was verified using RT-qPCR. Some studies have shown that Gas5 may induce arrest of PC12 cell proliferation by reversing C-myc, and cell cycle block (21). Gas5 can cause mouse embryonic hippocampal neuron progenitor cells (MK31) to exit the proliferation cycle and differentiate into neurons (22). Therefore, we suspect that Prx II may regulate DMSC neuronal differentiation through the Gas5/miRNA-34c-3p/mRNA (Syt1, Cntn2, and Mpp2) network. Neat1 has been shown to play an important role in neural stem cell differentiation (23), and Malat1 has been reported to promote neurite growth in N2a cells by activating ERK/MAPK signaling pathways (24). Combined with bioinformatics results, Malat1 and Neat1 may play a key role in Prx II regulation of neuronal differentiation. Whether Prx II regulates this network through molecular binding, protein post-translational modification or ROS needs to be further explored through experiments.

Conclusion

In summary, this study used DMSCs to explore the regulatory effect of Prx II on their differentiation to neurons and the related regulatory mechanisms. Through an analysis of the sequencing results of Prx II+/+ DMSCs and Prx II−/− DMSCs, 11 hub genes (Gria1, Nrcam, Sox10, Snap25, Cntn2, Dlg2, Ngf, Ntrk3, Amph, Syt1, and Cd24a), eight corresponding miRNAs (miRNA-466l, miRNA-34a, miRNA-185, miRNA-34b-5p, miRNA-34c, miRNA-449a, miRNA-449b, miRNA-449c) and 12 lncRNAs (Dubr, Gas5, Gm20427, Gm26917, Gm42547, Gm8066, Kcnq1ot1, Malat1, Mir17hg, Neat1, Rian, and Tug1) were. Elucidating the regulatory mechanism of Prx II in the process of MSC differentiation into neurons will improve the differentiation efficiency of stem cells and provide knowledge for promoting the recovery of neural function and delaying the progression of neurological diseases. Furthermore, the organic combination of DMSCs and gene modification technology can maximize the advantages of stem cell therapy and enable the improved application of stem cell technology in the clinic.

Acknowledgements

This work was supported by the Postgraduate Project to Innovate Scientific Research (YJSCX2021-Y102) from Heilongjiang Bayi Agricultural University and the Natural Science Foundation of Heilongjiang Province, China (LH2021C061).

Footnotes

  • Authors’ Contributions

    YHH, YYM, DHL, and TK conceived the study, wrote the manuscript, and conducted the literature search. XYX performed the data analysis. MHJ and HNS performed the analysis and quality assessment of the study. All Authors have read and approved the final version of the manuscript.

  • Funding

    This study was financially supported by Chonnam National University (Grant number: 2022-2731) and the National Research Foundation of Korea (NRF-2020R1G1A1102429, 2020R1I1A2052417).

  • Conflicts of Interest

    These Authors declare no conflicts of interest in relation to this study.

  • Received April 7, 2023.
  • Revision received May 4, 2023.
  • Accepted May 5, 2023.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

References

  1. ↵
    1. Badyra B,
    2. Sułkowski M,
    3. Milczarek O,
    4. Majka M
    : Mesenchymal stem cells as a multimodal treatment for nervous system diseases. Stem Cells Translational Medicine 9(10): 1174-1189, 2022. DOI: 10.1002/sctm.19-0430
    OpenUrlCrossRef
  2. ↵
    1. Sivandzade F,
    2. Cucullo L
    : Regenerative stem cell therapy for neurodegenerative diseases: an overview. International Journal of Molecular Sciences 22(4): 2153, 2021. DOI: 10.3390/ijms22042153
    OpenUrlCrossRef
  3. ↵
    1. Chang C,
    2. Chio C,
    3. Cheong C,
    4. Chao C,
    5. Cheng B,
    6. Lin M
    : Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury. Clinical Science 124(3): 165-176, 2021. DOI: 10.1042/CS20120226
    OpenUrlCrossRef
  4. ↵
    1. Ma S,
    2. Xie N,
    3. Li W,
    4. Yuan B,
    5. Shi Y,
    6. Wang Y
    : Immunobiology of mesenchymal stem cells. Cell Death & Differentiation 21(2): 216-225, 2021. DOI: 10.1038/cdd.2013.158
    OpenUrlCrossRef
  5. ↵
    1. Do P,
    2. Wu C,
    3. Chiang Y,
    4. Hu C,
    5. Chen K
    : Mesenchymal stem/stromal cell therapy in blood-brain barrier preservation following ischemia: molecular mechanisms and prospects. International Journal of Molecular Sciences 22(18): 10045, 2021. DOI: 10.3390/ijms221810045
    OpenUrlCrossRef
  6. ↵
    1. Donega V,
    2. Nijboer C,
    3. Van tilborg G,
    4. Dijkhuizen R,
    5. Kavelaars A,
    6. Heijnen C
    : Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury. Experimental Neurology 261: 53-64, 2022. DOI: 10.1016/j.expneurol.2014.06.009
    OpenUrlCrossRef
  7. ↵
    1. Abdullah R,
    2. Yaseen N,
    3. Salih S,
    4. Al-Juboory A,
    5. Hassan A,
    6. Al-Shammari A
    : Induction of mice adult bone marrow mesenchymal stem cells into functional motor neuron-like cells. Journal of Chemical Neuroanatomy 77: 129-142, 2019. DOI: 10.1016/j.jchemneu.2016.07.003
    OpenUrlCrossRef
  8. ↵
    1. Kim S,
    2. Park Y,
    3. Kim J,
    4. Sun H,
    5. Song I,
    6. Huang S,
    7. Lee S,
    8. Chae J,
    9. Hong S,
    10. Sik choi S,
    11. Choi S,
    12. Lee T,
    13. Kang S,
    14. Rhee S,
    15. Chang K,
    16. Lee S,
    17. Yu D,
    18. Lee D
    : Dominant role of peroxiredoxin/JNK axis in stemness regulation during neurogenesis from embryonic stem cells. Stem Cells 32(4): 998-1011, 2022. DOI: 10.1002/stem.1593
    OpenUrlCrossRef
  9. ↵
    1. Yang L,
    2. Cui Y,
    3. Sun X,
    4. Wang Y
    : Overexpression of TICRR and PPIF confer poor prognosis in endometrial cancer identified by gene co-expression network analysis. Aging 13(3): 4564-4589, 2021. DOI: 10.18632/aging.202417
    OpenUrlCrossRef
  10. ↵
    1. Zhao H,
    2. Wang D,
    3. Fu D,
    4. Xue L
    : Predicting the potential ankylosing spondylitis-related genes utilizing bioinformatics approaches. Rheumatology International 35(6): 973-979, 2019. DOI: 10.1007/s00296-014-3178-9
    OpenUrlCrossRef
  11. ↵
    1. Szklarczyk D,
    2. Morris JH,
    3. Cook H,
    4. Kuhn M,
    5. Wyder S,
    6. Simonovic M,
    7. Santos A,
    8. Doncheva NT,
    9. Roth A,
    10. Bork P,
    11. Jensen LJ,
    12. von Mering C
    : The string database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res 45(D1): D362-D368, 2017. DOI: 10.1093/nar/gkw937
    OpenUrlCrossRefPubMed
  12. ↵
    1. Yi X,
    2. Zhang B,
    3. Fu Y,
    4. Yi Z
    : STAT1 and its related molecules as potential biomarkers in Mycobacterium tuberculosis infection. Journal of Cellular and Molecular Medicine 24(5): 2866-2878, 2020. DOI: 10.1111/jcmm.14856
    OpenUrlCrossRef
  13. ↵
    1. Maqsood M,
    2. Kang M,
    3. Wu X,
    4. Chen J,
    5. Teng L,
    6. Qiu L
    : Adult mesenchymal stem cells and their exosomes: Sources, characteristics, and application in regenerative medicine. Life Sci 256: 118002, 2020. DOI: 10.1016/j.lfs.2020.118002
    OpenUrlCrossRef
  14. ↵
    1. Liu T
    : Application of mesenchymal stem cells derived from human pluripotent stem cells in regenerative medicine. World Journal of Stem Cells 13(12): 1826-1844, 2021. DOI: 10.4252/wjsc.v13.i12.1826
    OpenUrlCrossRef
  15. ↵
    1. Olguín-Albuerne M,
    2. Morán J
    : Redox signaling mechanisms in nervous system development. Antioxid Redox Signal 28(18): 1603-1625, 2018. DOI: 10.1089/ars.2017.7284
    OpenUrlCrossRef
  16. ↵
    1. Yan Y,
    2. Sabharwal P,
    3. Rao M,
    4. Sockanathan S
    : The antioxidant enzyme Prdx1 controls neuronal differentiation by thiol-redox-dependent activation of GDE2. Cell 138(6): 1209-1221, 2021. DOI: 10.1016/j.cell.2009.06.042
    OpenUrlCrossRef
  17. ↵
    1. Yan Y,
    2. Wladyka C,
    3. Fujii J,
    4. Sockanathan S
    : Prdx4 is a compartment-specific H2O2 sensor that regulates neurogenesis by controlling surface expression of GDE2. Nature Communications 6(1): 7006, 2023. DOI: 10.1038/ncomms8006
    OpenUrlCrossRef
  18. ↵
    1. Zhigang L,
    2. Crystal G,
    3. Tianyan W,
    4. Aimin L
    : Effect of peroxiredoxin 6 on proliferation and differentiation of bone marrow mesenchymal stem cells into neural lineage in vitro. CRTER 25(7): 1014-1018, 2021.
    OpenUrl
  19. ↵
    1. Han Y,
    2. Mao Y,
    3. Yu N,
    4. Jin M,
    5. Jin Y,
    6. Wang A,
    7. Zhang Y,
    8. Shen G,
    9. Cui Y,
    10. Yu L,
    11. Lee D,
    12. Jo Y,
    13. Sun H,
    14. Kwon J,
    15. Kwon T
    : RNA sequencing reveals that Prx II gene knockout can down-regulate the allograft rejection of dermal mesenchymal stem cells. Applied Biological Chemistry 63(1): 30, 2021. DOI: 10.1186/s13765-020-00515-z
    OpenUrlCrossRef
  20. ↵
    1. Thomson D,
    2. Dinger M
    : Endogenous microRNA sponges: evidence and controversy. Nature Reviews Genetics 17(5): 272-283, 2021. DOI: 10.1038/nrg.2016.20
    OpenUrlCrossRef
  21. ↵
    1. Jin G,
    2. Zhao H,
    3. Zhang S,
    4. Cheng X,
    5. Li H,
    6. Zhang L,
    7. He H,
    8. Qin J,
    9. Zhang W,
    10. Sun Y
    : Long non-coding RNA GAS5 promotes PC12 cells differentiation into Tuj1-positive neuron-like cells and induces cell cycle arrest. Neural Regeneration Research 14(12): 2118, 2022. DOI: 10.4103/1673-5374.262592
    OpenUrlCrossRef
  22. ↵
    1. Rozental R,
    2. Srinivas M,
    3. Gökhan S,
    4. Urban M,
    5. Dermietzel R,
    6. Kessler JA,
    7. Spray DC,
    8. Mehler MF
    : Temporal expression of neuronal connexins during hippocampal ontogeny. Brain Research Reviews 32(1): 57-71, 2020. DOI: 10.1016/s0165-0173(99)00096-x
    OpenUrlCrossRef
  23. ↵
    1. Mercer TR,
    2. Qureshi IA,
    3. Gokhan S,
    4. Dinger ME,
    5. Li G,
    6. Mattick JS,
    7. Mehler MF
    : Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation. BMC Neurosci 11: 14, 2010. DOI: 10.1186/1471-2202-11-14
    OpenUrlCrossRefPubMed
  24. ↵
    1. Chen L,
    2. Feng P,
    3. Zhu X,
    4. He S,
    5. Duan J,
    6. Zhou D
    : Long non-coding RNA Malat1 promotes neurite outgrowth through activation of ERK/MAPK signalling pathway in N2a cells. J Cell Mol Med 20(11): 2102-2110, 2016. DOI: 10.1111/jcmm.12904
    OpenUrlCrossRef
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Induction of Targeted Differentiation of Dermal Mesenchymal Stem Cells Into Neural Lineage According to Peroxiredoxin II Expression
YING-HAO HAN, XIAO-YA XING, DONG HUN LEE, YING-YING MAO, MEI-HUA JIN, HU-NAN SUN, TAEHO KWON
In Vivo Jul 2023, 37 (4) 1593-1602; DOI: 10.21873/invivo.13244
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