{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T13:06:28Z","timestamp":1774789588742,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,6,7]],"date-time":"2017-06-07T00:00:00Z","timestamp":1496793600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>A revolutionary approach that involves direct conversion of somatic cells into almost any other types of cells showed promising results for regenerative medicine. Currently, producing valuable cell types including neurons, cardiomyocytes, and hepatocytes through direct conversion of somatic cells appear to be a feasible option for regenerative medicine. The process involves inducing the cells by chemical cocktails or by expression of different types of transcription factors. In this concept, in vitro neurogenesis considered to be able to produce neuron cells to replace damaged neurons especially in Alzheimer and Parkinson disease. However, early successful experiments followed by major drawbacks such as low differentiation efficiency in producing neurons and detection of various undesirable types of cells in the culture. Therefore, there is not a single optimized common protocol for producing high quality neurons in vitro so far. This is partly due to the lack of our understanding about the precise cellular, genetic, and molecular mechanisms underlying neurogenesis via direct conversion. In the current work, we have employed meta\u2010analysis tools and extensive gene regulatory network analysis on the high throughput gene expression data obtained from previous reprogramming protocols to identify central gene regulatory components involved in direct conversion of fibroblasts into neurons. Our results identified miR\u20109, miR\u201030 as the most important miRNA and TP53, MYC, JUN, SP1, and SMAD2 considered to be the most important transcription factors. These findings would be useful for direct targeting these hub regulatory elements in order to increase the efficacy and specificity of the conversion protocols. J. Cell. Biochem. 118: 3158\u20133170, 2017. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.25944","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T10:56:40Z","timestamp":1487847400000},"page":"3158-3170","source":"Crossref","is-referenced-by-count":9,"title":["Dissection of Regulatory Elements During Direct Conversion of Somatic Cells Into Neurons"],"prefix":"10.1002","volume":"118","author":[{"given":"Tahereh","family":"Soleimani","sequence":"first","affiliation":[{"name":"Bioinformatics Lab Department of Biology School of Sciences Razi University Kermanshah Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nafiseh","family":"Falsafi","sequence":"additional","affiliation":[{"name":"Bioinformatics Lab Department of Biology School of Sciences Razi University Kermanshah Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8754-3491","authenticated-orcid":false,"given":"Hossein","family":"Fallahi","sequence":"additional","affiliation":[{"name":"Bioinformatics Lab Department of Biology School of Sciences Razi University Kermanshah Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,6,7]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05005"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.02.011"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10284"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2173"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-015-3400-8"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2294"},{"key":"e_1_2_5_9_1","first-page":"1","article-title":"MiR\u20109: A versatile regulator of neurogenesis","volume":"7","author":"Coolen M","year":"2015","journal-title":"Front Cell Neurosci"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3082"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.02.015"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2014.3642"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.106054"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.07.006"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1681"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001268"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.571"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110235"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000795"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27543"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.06.003"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3193"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-016-0001-8"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3278"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201489957"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1194"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2012.2095"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.198"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.06148-11"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605605103"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2016.07.014"},{"key":"e_1_2_5_33_1","first-page":"733733","article-title":"MiR\u201030 family controls proliferation and differentiation of intestinal epithelial cell models by directing a broad gene expression program that includes SOX9 and the ubiquitin ligase pathway","volume":"116","author":"Peck BC","year":"2016","journal-title":"J Biol Chem"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-7-20"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.05.018"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.446591"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2016.5203"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep15581"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-6-14"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.3402\/arb.v2.29244"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947601911410224"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5112"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8318"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/gtc.12009"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.14.3079"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18323"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2010.05.001"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2294"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1212769110"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1297-404"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.167"},{"key":"e_1_2_5_52_1","first-page":"802","article-title":"The microRNA\u2010520a\u20103p inhibits proliferation, apoptosis and metastasis by targeting MAP3K2 in non\u2010small cell lung cancer","volume":"5","author":"Yu J","year":"2015","journal-title":"Am J Cancer Res"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-014-0222-1"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2015.01.007"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2013.2627"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805562200"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.11.040"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.516112"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.25944","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.25944","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcb.25944","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.25944","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T01:01:49Z","timestamp":1740531709000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.25944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,7]]},"references-count":57,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1002\/jcb.25944"],"URL":"https:\/\/doi.org\/10.1002\/jcb.25944","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,7]]}}}