Promoting the Differentiation of Neural Progenitor Cells into Oligodendrocytes through the Induction of Olig2 Expression: A Transcriptomic Study Using RNA-seq Analysis
Oligodendrocytes are the myelinating cells of the central nervous system that facilitate efficient signal transduction. The loss of these cells and the associated myelin sheath can lead to profound functional deficits. Moreover, oligodendrocytes also play key roles in mediating glial-neuronal intera...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/9/1252 |
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| author | Katarzyna Pieczonka Mohamad Khazaei Michael G. Fehlings |
| author_facet | Katarzyna Pieczonka Mohamad Khazaei Michael G. Fehlings |
| author_sort | Katarzyna Pieczonka |
| collection | DOAJ |
| description | Oligodendrocytes are the myelinating cells of the central nervous system that facilitate efficient signal transduction. The loss of these cells and the associated myelin sheath can lead to profound functional deficits. Moreover, oligodendrocytes also play key roles in mediating glial-neuronal interactions, which further speaks to their importance in health and disease. Neural progenitor cells (NPCs) are a promising source of cells for the treatment of oligodendrocyte-related neurological diseases due to their ability to differentiate into a variety of cell types, including oligodendrocytes. However, the efficiency of oligodendrocyte differentiation is often low. In this study, we induced the expression of the Olig2 transcription factor in tripotent NPCs using a doxycycline-inducible promoter, such that the extent of oligodendrocyte differentiation could be carefully regulated. We characterized the differentiation profile and the transcriptome of these inducible oligodendrogenic NPCs (ioNPCs) using a combination of qRT-PCR, immunocytochemistry and RNA sequencing with gene ontology (GO) and gene set enrichment analysis (GSEA). Our results show that the ioNPCs differentiated into a significantly greater proportion of oligodendrocytes than the NPCs. The induction of Olig2 expression was also associated with the upregulation of genes involved in oligodendrocyte development and function, as well as the downregulation of genes involved in other cell lineages. The GO and GSEA analyses further corroborated the oligodendrocyte specification of the ioNPCs. |
| first_indexed | 2024-03-11T04:22:32Z |
| format | Article |
| id | doaj.art-b9341b67f2914a4f932bc0bb3e9767f3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T04:22:32Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b9341b67f2914a4f932bc0bb3e9767f32023-11-17T22:43:23ZengMDPI AGCells2073-44092023-04-01129125210.3390/cells12091252Promoting the Differentiation of Neural Progenitor Cells into Oligodendrocytes through the Induction of Olig2 Expression: A Transcriptomic Study Using RNA-seq AnalysisKatarzyna Pieczonka0Mohamad Khazaei1Michael G. Fehlings2Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, ON M5T 0S8, CanadaDivision of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, ON M5T 0S8, CanadaDivision of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, ON M5T 0S8, CanadaOligodendrocytes are the myelinating cells of the central nervous system that facilitate efficient signal transduction. The loss of these cells and the associated myelin sheath can lead to profound functional deficits. Moreover, oligodendrocytes also play key roles in mediating glial-neuronal interactions, which further speaks to their importance in health and disease. Neural progenitor cells (NPCs) are a promising source of cells for the treatment of oligodendrocyte-related neurological diseases due to their ability to differentiate into a variety of cell types, including oligodendrocytes. However, the efficiency of oligodendrocyte differentiation is often low. In this study, we induced the expression of the Olig2 transcription factor in tripotent NPCs using a doxycycline-inducible promoter, such that the extent of oligodendrocyte differentiation could be carefully regulated. We characterized the differentiation profile and the transcriptome of these inducible oligodendrogenic NPCs (ioNPCs) using a combination of qRT-PCR, immunocytochemistry and RNA sequencing with gene ontology (GO) and gene set enrichment analysis (GSEA). Our results show that the ioNPCs differentiated into a significantly greater proportion of oligodendrocytes than the NPCs. The induction of Olig2 expression was also associated with the upregulation of genes involved in oligodendrocyte development and function, as well as the downregulation of genes involved in other cell lineages. The GO and GSEA analyses further corroborated the oligodendrocyte specification of the ioNPCs.https://www.mdpi.com/2073-4409/12/9/1252neural progenitor cellsoligodendrocytesoligodendrocyte-related neurological diseasestranscription factor inductiontet-ON promotersdoxycycline |
| spellingShingle | Katarzyna Pieczonka Mohamad Khazaei Michael G. Fehlings Promoting the Differentiation of Neural Progenitor Cells into Oligodendrocytes through the Induction of Olig2 Expression: A Transcriptomic Study Using RNA-seq Analysis Cells neural progenitor cells oligodendrocytes oligodendrocyte-related neurological diseases transcription factor induction tet-ON promoters doxycycline |
| title | Promoting the Differentiation of Neural Progenitor Cells into Oligodendrocytes through the Induction of Olig2 Expression: A Transcriptomic Study Using RNA-seq Analysis |
| title_full | Promoting the Differentiation of Neural Progenitor Cells into Oligodendrocytes through the Induction of Olig2 Expression: A Transcriptomic Study Using RNA-seq Analysis |
| title_fullStr | Promoting the Differentiation of Neural Progenitor Cells into Oligodendrocytes through the Induction of Olig2 Expression: A Transcriptomic Study Using RNA-seq Analysis |
| title_full_unstemmed | Promoting the Differentiation of Neural Progenitor Cells into Oligodendrocytes through the Induction of Olig2 Expression: A Transcriptomic Study Using RNA-seq Analysis |
| title_short | Promoting the Differentiation of Neural Progenitor Cells into Oligodendrocytes through the Induction of Olig2 Expression: A Transcriptomic Study Using RNA-seq Analysis |
| title_sort | promoting the differentiation of neural progenitor cells into oligodendrocytes through the induction of olig2 expression a transcriptomic study using rna seq analysis |
| topic | neural progenitor cells oligodendrocytes oligodendrocyte-related neurological diseases transcription factor induction tet-ON promoters doxycycline |
| url | https://www.mdpi.com/2073-4409/12/9/1252 |
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