MicroRNA-375 Is Induced during Astrocyte-to-Neuron Reprogramming and Promotes Survival of Reprogrammed Neurons when Overexpressed
While astrocyte-to-neuron (AtN) reprogramming holds great promise in regenerative medicine, the molecular mechanisms that govern this unique biological process remain elusive. To understand the function of miRNAs during the AtN reprogramming process, we performed RNA-seq of both mRNAs and miRNAs on...
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MDPI AG
2023-09-01
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| author | Xuanyu Chen Ivan Sokirniy Xin Wang Mei Jiang Natalie Mseis-Jackson Christine Williams Kristopher Mayes Na Jiang Brendan Puls Quansheng Du Yang Shi Hedong Li |
| author_facet | Xuanyu Chen Ivan Sokirniy Xin Wang Mei Jiang Natalie Mseis-Jackson Christine Williams Kristopher Mayes Na Jiang Brendan Puls Quansheng Du Yang Shi Hedong Li |
| author_sort | Xuanyu Chen |
| collection | DOAJ |
| description | While astrocyte-to-neuron (AtN) reprogramming holds great promise in regenerative medicine, the molecular mechanisms that govern this unique biological process remain elusive. To understand the function of miRNAs during the AtN reprogramming process, we performed RNA-seq of both mRNAs and miRNAs on human astrocyte (HA) cultures upon NeuroD1 overexpression. Bioinformatics analyses showed that NeuroD1 not only activated essential neuronal genes to initiate the reprogramming process but also induced miRNA changes in HA. Among the upregulated miRNAs, we identified miR-375 and its targets, neuronal ELAVL genes (nELAVLs), which encode a family of RNA-binding proteins and were also upregulated by NeuroD1. We further showed that manipulating the miR-375 level regulated nELAVLs’ expression during NeuroD1-mediated reprogramming. Interestingly, miR-375/nELAVLs were also induced by the reprogramming factors Neurog2 and ASCL1 in HA, suggesting a conserved function to neuronal reprogramming, and by NeuroD1 in the mouse astrocyte culture and spinal cord. Functionally, we showed that miR-375 overexpression improved NeuroD1-mediated reprogramming efficiency by promoting cell survival at early stages in HA and did not appear to compromise the maturation of the reprogrammed neurons. Lastly, overexpression of miR-375-refractory ELAVL4 induced apoptosis and reversed the cell survival-promoting effect of miR-375 during AtN reprogramming. Together, we demonstrated a neuroprotective role of miR-375 during NeuroD1-mediated AtN reprogramming. |
| first_indexed | 2024-03-10T23:26:14Z |
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| id | doaj.art-e4c061c70b944d49b256fbe361f08f76 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T23:26:14Z |
| publishDate | 2023-09-01 |
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| series | Cells |
| spelling | doaj.art-e4c061c70b944d49b256fbe361f08f762023-11-19T07:58:38ZengMDPI AGCells2073-44092023-09-011217220210.3390/cells12172202MicroRNA-375 Is Induced during Astrocyte-to-Neuron Reprogramming and Promotes Survival of Reprogrammed Neurons when OverexpressedXuanyu Chen0Ivan Sokirniy1Xin Wang2Mei Jiang3Natalie Mseis-Jackson4Christine Williams5Kristopher Mayes6Na Jiang7Brendan Puls8Quansheng Du9Yang Shi10Hedong Li11Department of Neuroscience & Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Biomedical Engineering, The Pennsylvania State University, University Park, PA 16802, USADepartment of Biology, The Pennsylvania State University, University Park, PA 16802, USADepartment of Neuroscience & Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Neuroscience & Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Chemistry & Biochemistry, College of Science & Mathematics, Augusta University, Augusta, GA 30912, USADepartment of Neuroscience & Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Neuroscience & Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Biology, The Pennsylvania State University, University Park, PA 16802, USADepartment of Neuroscience & Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Neuroscience & Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA 30912, USADepartment of Neuroscience & Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA 30912, USAWhile astrocyte-to-neuron (AtN) reprogramming holds great promise in regenerative medicine, the molecular mechanisms that govern this unique biological process remain elusive. To understand the function of miRNAs during the AtN reprogramming process, we performed RNA-seq of both mRNAs and miRNAs on human astrocyte (HA) cultures upon NeuroD1 overexpression. Bioinformatics analyses showed that NeuroD1 not only activated essential neuronal genes to initiate the reprogramming process but also induced miRNA changes in HA. Among the upregulated miRNAs, we identified miR-375 and its targets, neuronal ELAVL genes (nELAVLs), which encode a family of RNA-binding proteins and were also upregulated by NeuroD1. We further showed that manipulating the miR-375 level regulated nELAVLs’ expression during NeuroD1-mediated reprogramming. Interestingly, miR-375/nELAVLs were also induced by the reprogramming factors Neurog2 and ASCL1 in HA, suggesting a conserved function to neuronal reprogramming, and by NeuroD1 in the mouse astrocyte culture and spinal cord. Functionally, we showed that miR-375 overexpression improved NeuroD1-mediated reprogramming efficiency by promoting cell survival at early stages in HA and did not appear to compromise the maturation of the reprogrammed neurons. Lastly, overexpression of miR-375-refractory ELAVL4 induced apoptosis and reversed the cell survival-promoting effect of miR-375 during AtN reprogramming. Together, we demonstrated a neuroprotective role of miR-375 during NeuroD1-mediated AtN reprogramming.https://www.mdpi.com/2073-4409/12/17/2202astrocytemicroRNAmiR-375miR-124NeuroD1neuronal reprogramming |
| spellingShingle | Xuanyu Chen Ivan Sokirniy Xin Wang Mei Jiang Natalie Mseis-Jackson Christine Williams Kristopher Mayes Na Jiang Brendan Puls Quansheng Du Yang Shi Hedong Li MicroRNA-375 Is Induced during Astrocyte-to-Neuron Reprogramming and Promotes Survival of Reprogrammed Neurons when Overexpressed Cells astrocyte microRNA miR-375 miR-124 NeuroD1 neuronal reprogramming |
| title | MicroRNA-375 Is Induced during Astrocyte-to-Neuron Reprogramming and Promotes Survival of Reprogrammed Neurons when Overexpressed |
| title_full | MicroRNA-375 Is Induced during Astrocyte-to-Neuron Reprogramming and Promotes Survival of Reprogrammed Neurons when Overexpressed |
| title_fullStr | MicroRNA-375 Is Induced during Astrocyte-to-Neuron Reprogramming and Promotes Survival of Reprogrammed Neurons when Overexpressed |
| title_full_unstemmed | MicroRNA-375 Is Induced during Astrocyte-to-Neuron Reprogramming and Promotes Survival of Reprogrammed Neurons when Overexpressed |
| title_short | MicroRNA-375 Is Induced during Astrocyte-to-Neuron Reprogramming and Promotes Survival of Reprogrammed Neurons when Overexpressed |
| title_sort | microrna 375 is induced during astrocyte to neuron reprogramming and promotes survival of reprogrammed neurons when overexpressed |
| topic | astrocyte microRNA miR-375 miR-124 NeuroD1 neuronal reprogramming |
| url | https://www.mdpi.com/2073-4409/12/17/2202 |
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