Stem Cells as a Good Tool to Investigate Dysregulated Biological Systems in Autism Spectrum Disorders

Carregando...
Imagem de Miniatura
Citações na Scopus
10
Tipo de produção
article
Data de publicação
2013
Editora
WILEY-BLACKWELL
Indexadores
Título da Revista
ISSN da Revista
Título do Volume
Autores
GRIESI-OLIVEIRA, Karina
SUNAGA, Daniele Yumi
ALVIZI, Lucas
PASSOS-BUENO, Maria Rita
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
AUTISM RESEARCH, v.6, n.5, p.354-361, 2013
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Identification of the causes of autism spectrum disorders (ASDs) is hampered by their genetic heterogeneity; however, the different genetic alterations leading to ASD seem to be implicated in the disturbance of common molecular pathways or biological processes. In this scenario, the search for differentially expressed genes (DEGs) between ASD patients and controls is a good alternative to identify the molecular etiology of such disorders. Here, we employed genome-wide expression analysis to compare the transcriptome of stem cells of human exfoliated deciduous teeth (SHEDs) of idiopathic autistic patients (n=7) and control samples (n=6). Nearly half of the 683 identified DEGs are expressed in the brain (P=0.003), and a significant number of them are involved in mechanisms previously associated with ASD such as protein synthesis, cytoskeleton regulation, cellular adhesion and alternative splicing, which validate the use of SHEDs to disentangle the causes of autism. Autistic patients also presented overexpression of genes regulated by androgen receptor (AR), and AR itself, which in turn interacts with CHD8 (chromodomain helicase DNA binding protein 8), a gene recently shown to be associated with the cause of autism and found to be upregulated in some patients tested here. These data provide a rationale for the mechanisms through which CHD8 leads to these diseases. In summary, our results suggest that ASD share deregulated pathways and revealed that SHEDs represent an alternative cell source to be used in the understanding of the biological mechanisms involved in the etiology of ASD. Autism Res 2013, ..: ..-... (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Palavras-chave
expression studies, androgen signaling, CHD8, stem cells of human exfoliated deciduous teeth
Referências
  1. Abrahams BS, 2008, NAT REV GENET, V9, P341, DOI 10.1038/nrg2346
  2. Anitha A, 2008, AM J MED GENET B, V147B, P1019, DOI 10.1002/ajmg.b.30697
  3. Baron CA, 2006, J AUTISM DEV DISORD, V36, P973, DOI 10.1007/s10803-006-0134-x
  4. Baron-Cohen S, 2005, SCIENCE, V310, P819, DOI 10.1126/science.1115455
  5. BENJAMINI Y, 1995, J ROY STAT SOC B MET, V57, P289
  6. Betancur C, 2009, TRENDS NEUROSCI, V32, P402, DOI 10.1016/j.tins.2009.04.003
  7. Betancur C, 2011, BRAIN RES, V1380, P42, DOI 10.1016/j.brainres.2010.11.078
  8. Breitling R, 2004, FEBS LETT, V573, P83, DOI 10.1016/j.febslet.2004.07.055
  9. Bueno DF, 2011, STEM CELL REV REP, V7, P446, DOI 10.1007/s12015-010-9197-3
  10. Buyske S., 2006, BMC GENET, V10, P8
  11. Campbell DB, 2007, ANN NEUROL, V62, P243, DOI 10.1002/ana.21180
  12. Campbell DB, 2008, AUTISM RES, V1, P159, DOI 10.1002/aur.27
  13. Chahrour M. H., 2012, PLOS GENETICS, V8
  14. Choi J, 2012, HUM MOL GENET, V21, P1566, DOI 10.1093/hmg/ddr594
  15. Cusco I, 2009, HUM MOL GENET, V18, P1795, DOI 10.1093/hmg/ddp092
  16. d'Aquino R, 2009, J EXP ZOOL PART B, V312B, P408, DOI 10.1002/jez.b.21263
  17. El-Fishawy P, 2010, PSYCHIAT CLIN N AM, V33, P83, DOI 10.1016/j.psc.2009.12.002
  18. Gkogkas CG, 2013, NATURE, V493, P371, DOI 10.1038/nature11628
  19. Gregg JP, 2008, GENOMICS, V91, P22, DOI 10.1016/j.ygeno.2007.09.003
  20. Hu VW, 2006, BMC GENOMICS, V7, DOI 10.1186/1471-2164-7-118
  21. Hu VW, 2009, PLOS ONE, V4, DOI 10.1371/journal.pone.0005775
  22. Hu VW, 2009, AUTISM RES, V2, P78, DOI 10.1002/aur.73
  23. Iossifov I, 2012, NEURON, V74, P285, DOI 10.1016/j.neuron.2012.04.009
  24. Irizarry RA, 2003, BIOSTATISTICS, V4, P249, DOI 10.1093/biostatistics/4.2.249
  25. Kelleher RJ, 2008, CELL, V135, P401, DOI 10.1016/j.cell.2008.10.017
  26. Levy D, 2011, NEURON, V70, P886, DOI 10.1016/j.neuron.2011.05.015
  27. Melin M, 2006, NEUROPSYCHOBIOLOGY, V54, P64, DOI 10.1159/000096040
  28. Costa AD, 2008, J CRANIOFAC SURG, V19, P204
  29. Menon T, 2010, MOL ENDOCRINOL, V24, P1165, DOI 10.1210/me.2009-0421
  30. Miura M, 2003, P NATL ACAD SCI USA, V100, P5807, DOI 10.1073/pnas.0937635100
  31. Morrow EM, 2008, SCIENCE, V321, P218, DOI 10.1126/science.1157657
  32. Neale BM, 2012, NATURE, V485, P242, DOI 10.1038/nature11011
  33. Neves-Pereira M, 2009, J MED GENET, V46, P759, DOI 10.1136/jmg.2009.066852
  34. Nishimura Y, 2007, HUM MOL GENET, V16, P1682, DOI 10.1093/hmg/ddm116
  35. Orabona GM, 2009, BRAIN RES, V1250, P14, DOI 10.1016/j.brainres.2008.11.007
  36. O'Roak BJ, 2011, NAT GENET, V43, P585, DOI 10.1038/ng.835
  37. O'Roak BJ, 2012, NATURE, V485, P246, DOI 10.1038/nature10989
  38. O'Roak BJ, 2012, SCIENCE, V338, P1619, DOI 10.1126/science.1227764
  39. Raj A, 2010, NATURE, V463, P913, DOI 10.1038/nature08781
  40. Russo A J, 2009, Biomark Insights, V4, P181
  41. Sanders SJ, 2012, NATURE, V485, P237, DOI 10.1038/nature10945
  42. Sarachana T, 2010, GENOME MED, V2, DOI 10.1186/gm144
  43. Sbacchi S, 2010, CURR GENOMICS, V11, P136, DOI 10.2174/138920210790886880
  44. Seno M. M. G., 2010, BRAIN RES, V1380, P85
  45. Smith Ryan M, 2011, Front Synaptic Neurosci, V3, P1, DOI 10.3389/fnsyn.2011.00001
  46. Sousa I, 2009, EUR J HUM GENET, V17, P749, DOI 10.1038/ejhg.2008.215
  47. Sugihara G, 2007, PROG NEURO-PSYCHOPH, V31, P412, DOI 10.1016/j.pnpbp.2006.10.010
  48. Talebizadeh Z, 2006, J MED GENET, V43, DOI 10.1136/jmg.2005.036897
  49. Talkowski ME, 2012, CELL, V149, DOI 10.1016/j.cell.2012.03.028
  50. Voineagu I, 2011, NATURE, V474, P380, DOI 10.1038/nature10110
  51. von Heydebreck A., 2004, BIOCONDUCTOR PROJECT
  52. Wang K, 2009, NATURE, V459, P528, DOI 10.1038/nature07999
  53. Xu LM, 2012, NUCLEIC ACIDS RES, V40, pD1016, DOI 10.1093/nar/gkr1145
  54. Yochum CL, 2010, BEHAV BRAIN RES, V210, P202, DOI 10.1016/j.bbr.2010.02.032