Paving the way to a neural fate – RNA signatures in naive and trans-differentiating mesenchymal stem cells
Mesenchymal Stem Cells (MSCs) derived from the embryonic mesoderm persist as a viable source of multipotent cells in adults and have a crucial role in tissue repair. One of the most promising aspects of MSCs is their ability to trans-differentiate into cell types outside of the mesodermal lineage, s...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | European Journal of Cell Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S017193352400075X |
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| author | Caroline Diener Konstantin Thüre Annika Engel Martin Hart Andreas Keller Eckart Meese Ulrike Fischer |
| author_facet | Caroline Diener Konstantin Thüre Annika Engel Martin Hart Andreas Keller Eckart Meese Ulrike Fischer |
| author_sort | Caroline Diener |
| collection | DOAJ |
| description | Mesenchymal Stem Cells (MSCs) derived from the embryonic mesoderm persist as a viable source of multipotent cells in adults and have a crucial role in tissue repair. One of the most promising aspects of MSCs is their ability to trans-differentiate into cell types outside of the mesodermal lineage, such as neurons. This characteristic positions MSCs as potential therapeutic tools for neurological disorders. However, the definition of a clear MSC signature is an ongoing topic of debate. Likewise, there is still a significant knowledge gap about functional alterations of MSCs during their transition to a neural fate. In this study, our focus is on the dynamic expression of RNA in MSCs as they undergo trans-differentiation compared to undifferentiated MSCs. To track and correlate changes in cellular signaling, we conducted high-throughput RNA expression profiling during the early time-course of human MSC neurogenic trans-differentiation. The expression of synapse maturation markers, including NLGN2 and NPTX1, increased during the first 24 h. The expression of neuron differentiation markers, such as GAP43 strongly increased during 48 h of trans-differentiation. Neural stem cell marker NES and neuron differentiation marker, including TUBB3 and ENO1, were highly expressed in mesenchymal stem cells and remained so during trans-differentiation. Pathways analyses revealed early changes in MSCs signaling that can be linked to the acquisition of neuronal features. Furthermore, we identified microRNAs (miRNAs) as potential drivers of the cellular trans-differentiation process. We also determined potential risk factors related to the neural trans-differentiation process. These factors include the persistence of stemness features and the expression of factors involved in neurofunctional abnormalities and tumorigenic processes. In conclusion, our findings contribute valuable insights into the intricate landscape of MSCs during neural trans-differentiation. These insights can pave the way for the development of safer treatments of neurological disorders. |
| format | Article |
| id | doaj-art-96732e78b88a43c481dd9cab8ebc7e84 |
| institution | OA Journals |
| issn | 0171-9335 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Cell Biology |
| spelling | doaj-art-96732e78b88a43c481dd9cab8ebc7e842025-08-20T02:38:58ZengElsevierEuropean Journal of Cell Biology0171-93352024-12-01103415145810.1016/j.ejcb.2024.151458Paving the way to a neural fate – RNA signatures in naive and trans-differentiating mesenchymal stem cellsCaroline Diener0Konstantin Thüre1Annika Engel2Martin Hart3Andreas Keller4Eckart Meese5Ulrike Fischer6Saarland University (USAAR), Institute of Human Genetics, Homburg 66421, GermanySaarland University (USAAR), Institute of Human Genetics, Homburg 66421, GermanySaarland University (USAAR), Chair for Clinical Bioinformatics, Saarbrücken 66123, Germany; Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarland University Campus, Saarbrücken 66123, GermanySaarland University (USAAR), Institute of Human Genetics, Homburg 66421, GermanySaarland University (USAAR), Chair for Clinical Bioinformatics, Saarbrücken 66123, Germany; Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarland University Campus, Saarbrücken 66123, GermanySaarland University (USAAR), Institute of Human Genetics, Homburg 66421, GermanySaarland University (USAAR), Institute of Human Genetics, Homburg 66421, Germany; Corresponding author.Mesenchymal Stem Cells (MSCs) derived from the embryonic mesoderm persist as a viable source of multipotent cells in adults and have a crucial role in tissue repair. One of the most promising aspects of MSCs is their ability to trans-differentiate into cell types outside of the mesodermal lineage, such as neurons. This characteristic positions MSCs as potential therapeutic tools for neurological disorders. However, the definition of a clear MSC signature is an ongoing topic of debate. Likewise, there is still a significant knowledge gap about functional alterations of MSCs during their transition to a neural fate. In this study, our focus is on the dynamic expression of RNA in MSCs as they undergo trans-differentiation compared to undifferentiated MSCs. To track and correlate changes in cellular signaling, we conducted high-throughput RNA expression profiling during the early time-course of human MSC neurogenic trans-differentiation. The expression of synapse maturation markers, including NLGN2 and NPTX1, increased during the first 24 h. The expression of neuron differentiation markers, such as GAP43 strongly increased during 48 h of trans-differentiation. Neural stem cell marker NES and neuron differentiation marker, including TUBB3 and ENO1, were highly expressed in mesenchymal stem cells and remained so during trans-differentiation. Pathways analyses revealed early changes in MSCs signaling that can be linked to the acquisition of neuronal features. Furthermore, we identified microRNAs (miRNAs) as potential drivers of the cellular trans-differentiation process. We also determined potential risk factors related to the neural trans-differentiation process. These factors include the persistence of stemness features and the expression of factors involved in neurofunctional abnormalities and tumorigenic processes. In conclusion, our findings contribute valuable insights into the intricate landscape of MSCs during neural trans-differentiation. These insights can pave the way for the development of safer treatments of neurological disorders.http://www.sciencedirect.com/science/article/pii/S017193352400075XMesenchymal stem cells (MSCs)Trans-differentiationNeuronTime-courseTranscriptomemiRnome |
| spellingShingle | Caroline Diener Konstantin Thüre Annika Engel Martin Hart Andreas Keller Eckart Meese Ulrike Fischer Paving the way to a neural fate – RNA signatures in naive and trans-differentiating mesenchymal stem cells European Journal of Cell Biology Mesenchymal stem cells (MSCs) Trans-differentiation Neuron Time-course Transcriptome miRnome |
| title | Paving the way to a neural fate – RNA signatures in naive and trans-differentiating mesenchymal stem cells |
| title_full | Paving the way to a neural fate – RNA signatures in naive and trans-differentiating mesenchymal stem cells |
| title_fullStr | Paving the way to a neural fate – RNA signatures in naive and trans-differentiating mesenchymal stem cells |
| title_full_unstemmed | Paving the way to a neural fate – RNA signatures in naive and trans-differentiating mesenchymal stem cells |
| title_short | Paving the way to a neural fate – RNA signatures in naive and trans-differentiating mesenchymal stem cells |
| title_sort | paving the way to a neural fate rna signatures in naive and trans differentiating mesenchymal stem cells |
| topic | Mesenchymal stem cells (MSCs) Trans-differentiation Neuron Time-course Transcriptome miRnome |
| url | http://www.sciencedirect.com/science/article/pii/S017193352400075X |
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