{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:54:52Z","timestamp":1786978492404,"version":"build-2736575974"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":1974,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Prenatal folic acid (FA) supplementation prevents neural tube defects. Folate receptor alpha (FR\u03b1) is critical for embryonic development, including neural crest (NC) development. Previously we showed that FR\u03b1 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 FR\u03b1 regulates stem cell characteristics of cranial neural crest cells (CNCCs)-critical for normal development. We hypothesized that FR\u03b1 upregulates coding genes and simultaneously downregulates non-coding miRNA which targets coding genes in CNCCs. Quantitative RT-PCR and chromatin immunoprecipitation showed that FR\u03b1 upregulates Oct4, Sox2, and Klf4 by binding to their cis-regulator elements-5\u2032 enhancer\/promoters defined by H3K27Ac and p300 occupancy. FA via FR\u03b1 downregulates miRNAs, miR-138 and miR-let-7, which target Oct4 and Trim71 (an Oct4 downstream effector), respectively. Co-immunoprecipitation data suggests that FR\u03b1 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\u2212\/\u2212), restored their proliferation potential. In summary, these results suggest a novel pleiotropic role of FR\u03b1: (a) direct activation of Oct4, Sox2, and Klf4 genes; and (b) repression of biogenesis of miRNAs that target these genes or their effector molecules.<\/jats:p>","DOI":"10.1002\/stem.2421","type":"journal-article","created":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T12:00:30Z","timestamp":1465905630000},"page":"2721-2732","source":"Crossref","is-referenced-by-count":47,"title":["Folate Receptor Alpha Upregulates\n                    <i>Oct4<\/i>\n                    ,\n                    <i>Sox2<\/i>\n                    and\n                    <i>Klf4<\/i>\n                    and Downregulates miR-138 and miR-let-7 in Cranial Neural Crest Cells"],"prefix":"10.1093","volume":"34","author":[{"given":"Vineet","family":"Mohanty","sequence":"first","affiliation":[{"name":"Developmental Biology Program, Stanley Manne Children's Research Institute, Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amar","family":"Shah","sequence":"additional","affiliation":[{"name":"Developmental Biology Program, Stanley Manne Children's Research Institute, Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Allender","sequence":"additional","affiliation":[{"name":"Developmental Biology Program, Stanley Manne Children's Research Institute, Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Rizwan","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Developmental Biology Program, Stanley Manne Children's Research Institute, Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Monick","sequence":"additional","affiliation":[{"name":"Developmental Biology Program, Stanley Manne Children's Research Institute, Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Ichi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Japanese Red Cross Medical Center, Shibuya-Ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Mania-Farnell","sequence":"additional","affiliation":[{"name":"Department of Biology, Purdue University at Calumet, Hammond, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"G. McLone","sequence":"additional","affiliation":[{"name":"Developmental Biology Program, Stanley Manne Children's Research Institute, Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadanori","family":"Tomita","sequence":"additional","affiliation":[{"name":"Developmental Biology Program, Stanley Manne Children's Research Institute, Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandra Shekhar","family":"Mayanil","sequence":"additional","affiliation":[{"name":"Developmental Biology Program, Stanley Manne Children's Research Institute, Division of Pediatric Neurosurgery, Ann and Robert H. 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