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miR-124, -128, and -137 Orchestrate Neural Differentiation by Acting on Overlapping Gene Sets Containing a Highly Connected Transcription Factor Network

Santos, Márcia C. T., Tegge, Allison N., Correa, Bruna R., Mahesula, Swetha, Kohnke, Luana Q., Qiao, Mei, Ferreira, Marco A. R., Kokovay, Erzsebet, Penalva, Luiz O. F.·2016·Stem Cells
DOI 10.1002/stem.2204
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Abstract

The ventricular-subventricular zone harbors neural stem cells (NSCs) that can differentiate into neurons, astrocytes, and oligodendrocytes. This process requires loss of stem cell properties and gain of characteristics associated with differentiated cells. miRNAs function as important drivers of this transition; miR-124, -128, and -137 are among the most relevant ones and have been shown to share commonalities and act as proneurogenic regulators. We conducted biological and genomic analyses to dissect their target repertoire during neurogenesis and tested the hypothesis that they act cooperatively to promote differentiation. To map their target genes, we transfected NSCs with antagomiRs and analyzed differences in their mRNA profile throughout differentiation with respect to controls. This strategy led to the identification of 910 targets for miR-124, 216 for miR-128, and 652 for miR-137. The target sets show extensive overlap. Inspection by gene ontology and network analysis indicated that transcription factors are a major component of these miRNAs target sets. Moreover, several of these transcription factors form a highly interconnected network. Sp1 was determined to be the main node of this network and was further investigated. Our data suggest that miR-124, -128, and -137 act synergistically to regulate Sp1 expression. Sp1 levels are dramatically reduced as cells differentiate and silencing of its expression reduced neuronal production and affected NSC viability and proliferation. In summary, our results show that miRNAs can act cooperatively and synergistically to regulate complex biological processes like neurogenesis and that transcription factors are heavily targeted to branch out their regulatory effect.

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Research works printed but not linked: 87

  1. Lim, 2014, Adult neural stem cells stake their ground, Trends Neurosci, 37, 563, 10.1016/j.tins.2014.08.006 · DOI
  2. Lazarini, 2011, Is adult neurogenesis essential for olfaction?, Trends Neurosci, 34, 20, 10.1016/j.tins.2010.09.006 · DOI
  3. Menn, 2006, Origin of oligodendrocytes in the subventricular zone of the adult brain, J Neurosci, 26, 7907, 10.1523/JNEUROSCI.1299-06.2006 · DOI · Paper page
  4. Sohn, 2015, The subventricular zone continues to generate corpus callosum and rostral migratory stream astroglia in normal adult mice, J Neurosci, 35, 3756, 10.1523/JNEUROSCI.3454-14.2015 · DOI
  5. Kawahara, 2012, MicroRNAs in Neural Stem Cells and Neurogenesis, Front Neurosci, 6, 30, 10.3389/fnins.2012.00030 · DOI
  6. Lang, 2012, Dynamic roles of microRNAs in Neurogenesis, Front Neurosci, 6, 71, 10.3389/fnins.2012.00071 · DOI
  7. Shi, 2010, MicroRNA regulation of neural stem cells and neurogenesis, J Neurosci, 30, 14931, 10.1523/JNEUROSCI.4280-10.2010 · DOI
  8. Gonzales-Roybal, 2013, Chromatin-based epigenetics of adult subventricular zone neural stem cells, Front Genet, 4, 194, 10.3389/fgene.2013.00194 · DOI
  9. Bian, 2011, Functions of noncoding RNAs in neural development and neurological diseases, Mol Neurobiol, 44, 359, 10.1007/s12035-011-8211-3 · DOI
  10. Motti, 2012, MicroRNAs and neuronal development, Semin Fetal Neonatal Med, 17, 347, 10.1016/j.siny.2012.07.008 · DOI
  11. Silber, 2008, miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells, BMC Med, 6, 14, 10.1186/1741-7015-6-14 · DOI · Paper page
  12. Enciu, 2012, MicroRNAs in brain development and degeneration, Mol Biol Rep, 39, 2243, 10.1007/s11033-011-0973-1 · DOI
  13. Saba, 2008, A miRNA signature of prion induced neurodegeneration, PLoS One, 3, e3652, 10.1371/journal.pone.0003652 · DOI · Paper page
  14. Tan, 2013, MicroRNA-128 governs neuronal excitability and motor behavior in mice, Science, 342, 1254, 10.1126/science.1244193 · DOI · Paper page
  15. Wright, 2013, Potential impact of miR-137 and its targets in schizophrenia, Front Genet, 4, 58, 10.3389/fgene.2013.00058 · DOI
  16. Cheng, 2009, miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche, Nat Neurosci, 12, 399, 10.1038/nn.2294 · DOI · Paper page
  17. Gascon, 2014, Alterations in microRNA-124 and AMPA receptors contribute to social behavioral deficits in frontotemporal dementia, Nat Med, 20, 1444, 10.1038/nm.3717 · DOI · Paper page
  18. Johnson, 2009, Gene dysregulation in Huntington's disease: REST, microRNAs and beyond, Neuromol Med, 11, 183, 10.1007/s12017-009-8063-4 · DOI
  19. Lee, 2011, Altered microRNA regulation in Huntington's disease models, Exp Neurol, 227, 172, 10.1016/j.expneurol.2010.10.012 · DOI · Paper page
  20. Muinos-Gimeno, 2009, Allele variants in functional MicroRNA target sites of the neurotrophin-3 receptor gene (NTRK3) as susceptibility factors for anxiety disorders, Hum Mutat, 30, 1062, 10.1002/humu.21005 · DOI
  21. Bruno, 2011, Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay, Mol Cell, 42, 500, 10.1016/j.molcel.2011.04.018 · DOI
  22. Smalheiser, 2014, Expression of microRNAs and other small RNAs in prefrontal cortex in schizophrenia, bipolar disorder and depressed subjects, PLoS One, 9, e86469, 10.1371/journal.pone.0086469 · DOI
  23. Soldati, 2013, Dysregulation of REST-regulated coding and non-coding RNAs in a cellular model of Huntington's disease, J Neurochem, 124, 418, 10.1111/jnc.12090 · DOI
  24. Tamim, 2014, Genomic analyses reveal broad impact of miR-137 on genes associated with malignant transformation and neuronal differentiation in glioblastoma cells, PLoS One, 9, e85591, 10.1371/journal.pone.0085591 · DOI
  25. Livak, 2001, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method, Methods, 25, 402, 10.1006/meth.2001.1262 · DOI · Paper page
  26. Trapnell, 2012, Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks, Nat Protoc, 7, 562, 10.1038/nprot.2012.016 · DOI
  27. Trapnell, 2009, TopHat: Discovering splice junctions with RNA-Seq, Bioinformatics, 25, 1105, 10.1093/bioinformatics/btp120 · DOI
  28. Trapnell, 2010, Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation, Nat Biotechnol, 28, 511, 10.1038/nbt.1621 · DOI · Paper page
  29. Abernathy, 2015, MicroRNA-dependent genetic networks during neural development, Cell Tissue Res, 359, 179, 10.1007/s00441-014-1899-4 · DOI
  30. Benjamini, 1995, Controlling the false discovery rate—A practical and powerful approach to multiple testing, J R Stat Soc Ser B-Methodol, 57, 289, 10.1111/j.2517-6161.1995.tb02031.x · DOI · Paper page
  31. Lewis, 2003, Prediction of mammalian microRNA targets, Cell, 115, 787, 10.1016/S0092-8674(03)01018-3 · DOI · Paper page
  32. John, 2004, Human MicroRNA targets, PLoS Biol, 2, e363, 10.1371/journal.pbio.0020363 · DOI · Paper page
  33. Hsu, 2014, miRTarBase update 2014: An information resource for experimentally validated miRNA-target interactions, Nucleic Acids Res, 42, D78, 10.1093/nar/gkt1266 · DOI
  34. Carter, 1988, A statistical approach to the construction and analysis of isobolograms, J Am Coll Toxicol, 7
  35. Feng PaK, 2004, An extension of the model free test to test synergy in multiple drug combinations, Biometric J, 46, 293, 10.1002/bimj.200310038 · DOI
  36. Laska, 1994, Simple designs and model-free tests for synergy, Biometrics, 50, 834, 10.2307/2532796 · DOI
  37. Guan, 2012, Sp1 is upregulated in human glioma, promotes MMP-2-mediated cell invasion and predicts poor clinical outcome, Int J Cancer, 130, 593, 10.1002/ijc.26049 · DOI
  38. Luo, 2015, Transcriptional factor specificity protein 1 (SP1) promotes the proliferation of glioma cells by up-regulating midkine (MDK), Mol Biol Cell, 26, 430, 10.1091/mbc.E14-10-1443 · DOI
  39. Neph, 2012, An expansive human regulatory lexicon encoded in transcription factor footprints, Nature, 489, 83, 10.1038/nature11212 · DOI
  40. Wang, 2012, Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors, Genome Res, 22, 1798, 10.1101/gr.139105.112 · DOI
  41. Meza-Sosa, 2014, microRNAs: Key triggers of neuronal cell fate, Front Cell Neurosci, 8, 175, 10.3389/fncel.2014.00175 · DOI
  42. Follert, 2014, MicroRNAs in brain development and function: A matter of flexibility and stability, Front Mol Neurosci, 7, 5, 10.3389/fnmol.2014.00005 · DOI
  43. Sun, 2013, MicroRNAs: Regulators of neuronal fate, Curr Opin Cell Biol, 25, 215, 10.1016/j.ceb.2012.12.007 · DOI
  44. Krichevsky, 2006, Specific microRNAs modulate embryonic stem cell-derived neurogenesis, Stem Cells, 24, 857, 10.1634/stemcells.2005-0441 · DOI · Paper page
  45. Neo, 2014, MicroRNA miR-124 controls the choice between neuronal and astrocyte differentiation by fine-tuning Ezh2 expression, J Biol Chem, 289, 20788, 10.1074/jbc.M113.525493 · DOI
  46. Weng, 2012, Drosophila miR-124 regulates neuroblast proliferation through its target anachronism, Development, 139, 1427, 10.1242/dev.075143 · DOI
  47. Liu, 2011, MiR-124 regulates early neurogenesis in the optic vesicle and forebrain, targeting NeuroD1, Nucleic Acids Res, 39, 2869, 10.1093/nar/gkq904 · DOI
  48. Visvanathan, 2007, The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development, Genes Dev, 21, 744, 10.1101/gad.1519107 · DOI · Paper page
  49. Makeyev, 2007, The microRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing, Mol Cell, 27, 435, 10.1016/j.molcel.2007.07.015 · DOI · Paper page
  50. Sun, 2011, miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells, Nat Commun, 2, 529, 10.1038/ncomms1532 · DOI
  51. Li, 2014, Computational prediction of microRNA networks incorporating environmental toxicity and disease etiology, Sci Rep, 4, 5576, 10.1038/srep05576 · DOI
  52. Takahashi, 2014, The role of microRNAs in the regulation of cancer stem cells, Front Genet, 4, 295, 10.3389/fgene.2013.00295 · DOI · Paper page
  53. Dong, 2010, MicroRNA networks in mouse lung organogenesis, PLoS One, 5, e10854, 10.1371/journal.pone.0010854 · DOI
  54. Volinia, 2010, Reprogramming of miRNA networks in cancer and leukemia, Genome Res, 20, 589, 10.1101/gr.098046.109 · DOI
  55. Na, 2013, Understanding cooperativity of microRNAs via microRNA association networks, BMC Genomics, 14, S17, 10.1186/1471-2164-14-S5-S17 · DOI
  56. Gao, 2008, Posttranscriptional control of neuronal development by microRNA networks, Trends Neurosci, 31, 20, 10.1016/j.tins.2007.10.004 · DOI
  57. Chen, 2010, miR-7 and miR-214 are specifically expressed during neuroblastoma differentiation, cortical development and embryonic stem cells differentiation, and control neurite outgrowth in vitro, Biochem Biophys Res Commun, 394, 921, 10.1016/j.bbrc.2010.03.076 · DOI
  58. Morgado, 2015, MicroRNA-34a modulates neural stem cell differentiation by regulating expression of synaptic and autophagic proteins, Mol Neurobiol, 51, 1168, 10.1007/s12035-014-8794-6 · DOI
  59. Aranha, 2011, miR-34a regulates mouse neural stem cell differentiation, PLoS One, 6, e21396, 10.1371/journal.pone.0021396 · DOI
  60. Martinez, 2008, A C. elegans genome-scale microRNA network contains composite feedback motifs with high flux capacity, Genes Dev, 22, 2535, 10.1101/gad.1678608 · DOI
  61. Martinez, 2009, The interplay between transcription factors and microRNAs in genome-scale regulatory networks, Bioessays, 31, 435, 10.1002/bies.200800212 · DOI
  62. Guo, 2014, Genome-wide survey of tissue-specific microRNA and transcription factor regulatory networks in 12 tissues, Sci Rep, 4, 5150, 10.1038/srep05150 · DOI · Paper page
  63. Busskamp, 2014, Rapid neurogenesis through transcriptional activation in human stem cells, Mol Syst Biol, 10, 760, 10.15252/msb.20145508 · DOI
  64. Wu, 2006, Comparative sequence analysis reveals an intricate network among REST, CREB and miRNA in mediating neuronal gene expression, Genome Biol, 7, R85, 10.1186/gb-2006-7-9-r85 · DOI · Paper page
  65. Zhou, 2007, Impaired postnatal development of hippocampal dentate gyrus in Sp4 null mutant mice, Genes Brain Behav, 6, 269, 10.1111/j.1601-183X.2006.00256.x · DOI
  66. Pinacho, 2014, Increased SP4 and SP1 transcription factor expression in the postmortem hippocampus of chronic schizophrenia, J Psychiatr Res, 58, 189, 10.1016/j.jpsychires.2014.08.006 · DOI
  67. Zhou, 2009, Transcription factor SP4 is a susceptibility gene for bipolar disorder, PLoS One, 4, e5196, 10.1371/journal.pone.0005196 · DOI
  68. Tam, 2010, Confirmed rare copy number variants implicate novel genes in schizophrenia, Biochem Soc Trans, 38, 445, 10.1042/BST0380445 · DOI · Paper page
  69. Chandran, 2014, Disc1 variation leads to specific alterations in adult neurogenesis, PLoS One, 9, e108088, 10.1371/journal.pone.0108088 · DOI
  70. Mao, 2009, Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3beta/beta-catenin signaling, Cell, 136, 1017, 10.1016/j.cell.2008.12.044 · DOI
  71. Giachino, 2005, cAMP response element-binding protein regulates differentiation and survival of newborn neurons in the olfactory bulb, J Neurosci, 25, 10105, 10.1523/JNEUROSCI.3512-05.2005 · DOI
  72. Kandasamy, 2014, TGF-beta signalling in the adult neurogenic niche promotes stem cell quiescence as well as generation of new neurons, J Cell Mol Med, 18, 1444, 10.1111/jcmm.12298 · DOI
  73. Miguez, 2013, Smad2 and Smad3 cooperate and antagonize simultaneously in vertebrate neurogenesis, J Cell Sci, 126, 5335
  74. Kadonaga, 1987, Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain, Cell, 51, 1079, 10.1016/0092-8674(87)90594-0 · DOI
  75. Karlseder, 1996, Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F, Mol Cell Biol, 16, 1659, 10.1128/MCB.16.4.1659 · DOI
  76. Lin, 1996, Cell cycle-regulated association of E2F1 and Sp1 is related to their functional interaction, Mol Cell Biol, 16, 1668, 10.1128/MCB.16.4.1668 · DOI
  77. Hirose, 2013, An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways, Nature, 500, 354, 10.1038/nature12329 · DOI
  78. Khan, 2003, Estrogen receptor/Sp1 complexes are required for induction of cad gene expression by 17beta-estradiol in breast cancer cells, Endocrinology, 144, 2325, 10.1210/en.2002-0149 · DOI
  79. Duttenhoefer, 2014, Sp1-dependent regulation of PPARalpha in bone metabolism, Int J Oral Maxillofac Implants, 29, e107, 10.11607/jomi.te49 · DOI
  80. Chen, 2014, JWA suppresses tumor angiogenesis via Sp1-activated matrix metalloproteinase-2 and its prognostic significance in human gastric cancer, Carcinogenesis, 35, 442, 10.1093/carcin/bgt311 · DOI
  81. Wei, 2004, Celecoxib inhibits vascular endothelial growth factor expression in and reduces angiogenesis and metastasis of human pancreatic cancer via suppression of Sp1 transcription factor activity, Cancer Res, 64, 2030, 10.1158/0008-5472.CAN-03-1945 · DOI
  82. Hsu, 2012, Sp1 expression regulates lung tumor progression, Oncogene, 31, 3973, 10.1038/onc.2011.568 · DOI
  83. Jungert, 2007, Sp1 is required for transforming growth factor-beta-induced mesenchymal transition and migration in pancreatic cancer cells, Cancer Res, 67, 1563, 10.1158/0008-5472.CAN-06-1670 · DOI
  84. Elmi, 2010, TLX activates MASH1 for induction of neuronal lineage commitment of adult hippocampal neuroprogenitors, Mol Cell Neurosci, 45, 121, 10.1016/j.mcn.2010.06.003 · DOI
  85. Dunah, 2002, Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease, Science, 296, 2238, 10.1126/science.1072613 · DOI
  86. Dong, 2014, An axis involving SNAI1, microRNA-128 and SP1 modulates glioma progression, PLoS One, 9, e98651, 10.1371/journal.pone.0098651 · DOI
  87. Mondanizadeh, 2015, MicroRNA-124 regulates neuronal differentiation of mesenchymal stem cells by targeting Sp1 mRNA, J Cell Biochem, 116, 943, 10.1002/jcb.25045 · DOI

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Metadata

Authors
Santos, M. C. T., Tegge, A. N., Correa, B. R., Mahesula, S., Kohnke, L. Q., Qiao, M., Ferreira, M. A. R., Kokovay, E., & Penalva, L. O. F.
Affiliations
  • Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
  • Department of Computer Science, Virginia Tech, Blacksburg, Virginia, USA
  • Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
  • Department of Statistics, Virginia Tech, Blacksburg, Virginia, USA
Venue
Stem Cells
Publisher
Oxford University Press (OUP)
Published
2015-09-15
Volume
34
Issue
1
Pages
220-232
ISSN
  • 1066-5099
  • 1549-4918
DOI
10.1002/stem.2204
Cited by
57
References
6
Language
en
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Funders
  • FAPESP (2011/51588-2, 2012/22950-8, 2013/25483-4)
  • Sam and Ann Barshop Aging Institute
  • Center for Biomedical Neuroscience (UTHSCSA)

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