| First Author | Mohanty V | Year | 2016 |
| Journal | Stem Cells | Volume | 34 |
| Issue | 11 | Pages | 2721-2732 |
| PubMed ID | 27300003 | Mgi Jnum | J:238291 |
| Mgi Id | MGI:5819003 | Doi | 10.1002/stem.2421 |
| Citation | Mohanty V, et al. (2016) Folate Receptor Alpha Upregulates Oct4, Sox2 and Klf4 and Downregulates miR-138 and miR-let-7 in Cranial Neural Crest Cells. Stem Cells 34(11):2721-2732 |
| abstractText | Prenatal folic acid (FA) supplementation prevents neural tube defects. Folate receptor alpha (FRalpha) is critical for embryonic development, including neural crest (NC) development. Previously we showed that FRalpha translocates to the nucleus in response to FA, where it acts as a transcription factor. In this study, we examined if FA through interaction with FRalpha regulates stem cell characteristics of cranial neural crest cells (CNCCs)-critical for normal development. We hypothesized that FRalpha upregulates coding genes and simultaneously downregulates non-coding miRNA which targets coding genes in CNCCs. Quantitative RT-PCR and chromatin immunoprecipitation showed that FRalpha upregulates Oct4, Sox2, and Klf4 by binding to their cis-regulator elements-5' enhancer/promoters defined by H3K27Ac and p300 occupancy. FA via FRalpha downregulates miRNAs, miR-138 and miR-let-7, which target Oct4 and Trim71 (an Oct4 downstream effector), respectively. Co-immunoprecipitation data suggests that FRalpha interacts with the Drosha-DGCR8 complex to affect pre-miRNA processing. Transfecting anti-miR-138 or anti-miR-let-7 into non-proliferating neural crest cells (NCCs) derived from Splotch (Sp(-/-) ), restored their proliferation potential. In summary, these results suggest a novel pleiotropic role of FRalpha: (a) direct activation of Oct4, Sox2, and Klf4 genes; and (b) repression of biogenesis of miRNAs that target these genes or their effector molecules. Stem Cells 2016;34:2721-2732. |
