| Title: |
MiR-375 is Essential for Human Spinal Motor Neuron Development and May Be Involved in Motor Neuron Degeneration |
| Authors: |
Bhinge, Akshay; Namboori, Seema C.; Bithell, Angela; Soldati, Chiara; Buckley, Noel J.; Stanton, Lawrence W. |
| Contributors: |
A*STAR, Singapore |
| Source: |
Stem Cells ; volume 34, issue 1, page 124-134 ; ISSN 1066-5099 1549-4918 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2015 |
| Description: |
The transcription factor REST is a key suppressor of neuronal genes in non-neuronal tissues. REST has been shown to suppress proneuronal microRNAs in neural progenitors indicating that REST-mediated neurogenic suppression may act in part via microRNAs. We used neural differentiation of Rest-null mouse ESC to identify dozens of microRNAs regulated by REST during neural development. One of the identified microRNAs, miR-375, was upregulated during human spinal motor neuron development. We found that miR-375 facilitates spinal motor neurogenesis by targeting the cyclin kinase CCND2 and the transcription factor PAX6. Additionally, miR-375 inhibits the tumor suppressor p53 and protects neurons from apoptosis in response to DNA damage. Interestingly, motor neurons derived from a spinal muscular atrophy patient displayed depressed miR-375 expression and elevated p53 protein levels. Importantly, SMA motor neurons were significantly more susceptible to DNA damage induced apoptosis suggesting that miR-375 may play a protective role in motor neurons. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/stem.2233 |
| Availability: |
https://doi.org/10.1002/stem.2233; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fstem.2233; https://onlinelibrary.wiley.com/doi/pdf/10.1002/stem.2233; https://onlinelibrary.wiley.com/doi/full-xml/10.1002/stem.2233; https://academic.oup.com/stmcls/article-pdf/34/1/124/42026081/stmcls_34_1_124.pdf |
| Rights: |
https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model |
| Accession Number: |
edsbas.FCDF6613 |
| Database: |
BASE |