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Su C, Argenziano M, Lu S, et al. 3D promoter architecture re-organization during iPSC-derived neuronal cell differentiation implicates target genes for neurodevelopmental disorders. Prog Neurobiol. 2021;201:102000doi: 10.1016/j.pneurobio.2021.102000.
Su, C., Argenziano, M., Lu, S., Pippin, J. A., Pahl, M. C., Leonard, M. E., Cousminer, D. L., Johnson, M. E., Lasconi, C., Wells, A. D., Chesi, A., & Grant, S. F. A. (2021). 3D promoter architecture re-organization during iPSC-derived neuronal cell differentiation implicates target genes for neurodevelopmental disorders. Progress in neurobiology, 201102000. https://doi.org/10.1016/j.pneurobio.2021.102000
Su, Chun, et al. "3D promoter architecture re-organization during iPSC-derived neuronal cell differentiation implicates target genes for neurodevelopmental disorders." Progress in neurobiology vol. 201 (2021): 102000. doi: https://doi.org/10.1016/j.pneurobio.2021.102000
Su C, Argenziano M, Lu S, Pippin JA, Pahl MC, Leonard ME, Cousminer DL, Johnson ME, Lasconi C, Wells AD, Chesi A, Grant SFA. 3D promoter architecture re-organization during iPSC-derived neuronal cell differentiation implicates target genes for neurodevelopmental disorders. Prog Neurobiol. 2021 Jun;201:102000. doi: 10.1016/j.pneurobio.2021.102000. Epub 2021 Feb 02. PMID: 33545232; PMCID: PMC8096691.
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Prog Neurobiol. 2021 Jun;201:102000. doi: 10.1016/j.pneurobio.2021.102000. Epub 2021 Feb 02.

3D promoter architecture re-organization during iPSC-derived neuronal cell differentiation implicates target genes for neurodevelopmental disorders.

Progress in neurobiology

Chun Su, Mariana Argenziano, Sumei Lu, James A Pippin, Matthew C Pahl, Michelle E Leonard, Diana L Cousminer, Matthew E Johnson, Chiara Lasconi, Andrew D Wells, Alessandra Chesi, Struan F A Grant

Affiliations

  1. Division of Human Genetics, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA, United States.
  2. Heart Institute, University of South Florida, 560 Channelside Dr, Tampa FL 33602, United States.
  3. Department of Pathology, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA, United States; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 3615 Civic Center Boulevard, Philadelphia, PA, United States.
  4. Division of Human Genetics, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA, United States; Division of Diabetes and Endocrinology, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA, United States; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, 3615 Civic Center Boulevard, Philadelphia, PA, United States; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, 3615 Civic Center Boulevard, Philadelphia, PA, United States. Electronic address: [email protected].

PMID: 33545232 PMCID: PMC8096691 DOI: 10.1016/j.pneurobio.2021.102000

Abstract

Neurodevelopmental disorders are thought to arise from interrupted development of the brain at an early age. Genome-wide association studies (GWAS) have identified hundreds of loci associated with susceptibility to neurodevelopmental disorders; however, which noncoding variants regulate which genes at these loci is often unclear. To implicate neuronal GWAS effector genes, we performed an integrated analysis of transcriptomics, epigenomics and chromatin conformation changes during the development from Induced pluripotent stem cell-derived neuronal progenitor cells (NPCs) into neurons using a combination of high-resolution promoter-focused Capture-C, ATAC-seq and RNA-seq. We observed that gene expression changes during the NPC-to-neuron transition were highly dependent on both promoter accessibility changes and long-range interactions which connect distal cis-regulatory elements (enhancer or silencers) to developmental-stage-specific genes. These genome-scale promoter-cis-regulatory-element atlases implicated 454 neurodevelopmental disorder-associated, putative causal variants mapping to 600 distal targets. These putative effector genes were significantly enriched for pathways involved in the regulation of neuronal development and chromatin organization, with 27 % expressed in a stage-specific manner. The intersection of open chromatin and chromatin conformation revealed development-stage-specific gene regulatory architectures during neuronal differentiation, providing a rich resource to aid characterization of the genetic and developmental basis of neurodevelopmental disorders.

Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Keywords: Chromatin architecture; Epigenomics; Neurodevelopmental disorders; iPSC

References

  1. JAMA Psychiatry. 2015 May;72(5):415-23 - PubMed
  2. Elife. 2018 Jul 10;7: - PubMed
  3. Nature. 2014 Jul 24;511(7510):421-7 - PubMed
  4. F1000Res. 2015 Nov 20;4:1310 - PubMed
  5. OMICS. 2013 Jun;17(6):283-96 - PubMed
  6. Bioinformatics. 2010 Mar 15;26(6):841-2 - PubMed
  7. Nat Commun. 2015 Aug 18;6:7973 - PubMed
  8. Biol Psychiatry. 2005 Jun 1;57(11):1313-23 - PubMed
  9. Bioinformatics. 2015 Jan 15;31(2):166-9 - PubMed
  10. Arch Gen Psychiatry. 2003 May;60(5):497-502 - PubMed
  11. PLoS Comput Biol. 2015 Apr 17;11(4):e1004219 - PubMed
  12. Nat Genet. 2011 Mar;43(3):264-8 - PubMed
  13. Arch Gen Psychiatry. 1987 Jul;44(7):660-9 - PubMed
  14. Nat Commun. 2020 Jul 3;11(1):3294 - PubMed
  15. Genome Biol. 2016 Jun 15;17(1):127 - PubMed
  16. J Neurosci. 2005 Apr 27;25(17):4353-64 - PubMed
  17. Nat Commun. 2018 Jan 15;9(1):189 - PubMed
  18. FASEB J. 2018 Apr;32(4):1830-1840 - PubMed
  19. Bioinformatics. 2019 Nov 1;35(22):4764-4766 - PubMed
  20. Transl Psychiatry. 2016 Feb 09;6:e731 - PubMed
  21. Nucleic Acids Res. 2020 Jan 8;48(D1):D87-D92 - PubMed
  22. Mol Cell Neurosci. 2008 Aug;38(4):616-28 - PubMed
  23. Nat Genet. 2019 Jan;51(1):63-75 - PubMed
  24. Genes Dev. 2002 Oct 15;16(20):2699-712 - PubMed
  25. Nat Commun. 2019 Mar 19;10(1):1260 - PubMed
  26. Genome Res. 2017 Nov;27(11):1939-1949 - PubMed
  27. Nat Genet. 2004 Aug;36(8):900-5 - PubMed
  28. Stem Cell Res. 2016 Mar;16(2):338-41 - PubMed
  29. Nucleic Acids Res. 2016 Mar 18;44(5):e45 - PubMed
  30. Cell. 2019 Aug 8;178(4):850-866.e26 - PubMed
  31. Nucleic Acids Res. 2019 Jan 25;47(2):e11 - PubMed
  32. Mol Psychiatry. 2018 May;23(5):1181-1188 - PubMed
  33. Bioinformatics. 2015 Dec 1;31(23):3847-9 - PubMed
  34. Elife. 2017 Mar 23;6: - PubMed
  35. Stem Cell Reports. 2017 Nov 14;9(5):1530-1545 - PubMed
  36. Cell. 2016 Nov 17;167(5):1369-1384.e19 - PubMed
  37. Neuron. 2008 Feb 7;57(3):378-92 - PubMed
  38. Arch Gen Psychiatry. 2003 Dec;60(12):1187-92 - PubMed
  39. Nat Biotechnol. 2015 Apr;33(4):364-76 - PubMed
  40. Nat Biotechnol. 2014 Feb;32(2):171-178 - PubMed
  41. Curr Opin Psychiatry. 2014 Mar;27(2):95-7 - PubMed
  42. Cell. 2000 May 12;101(4):425-33 - PubMed
  43. Organogenesis. 2007 Oct;3(2):93-101 - PubMed
  44. Nucleic Acids Res. 2007 Jan;35(Database issue):D88-92 - PubMed
  45. Nat Commun. 2015 Jan 19;6:5890 - PubMed
  46. Bioinformatics. 2010 Jan 1;26(1):139-40 - PubMed
  47. Development. 2017 Oct 15;144(20):3686-3697 - PubMed
  48. Nat Genet. 2019 Aug;51(8):1252-1262 - PubMed
  49. Hum Mol Genet. 2017 May 15;26(10):1942-1951 - PubMed
  50. Nat Methods. 2012 Mar 04;9(4):357-9 - PubMed
  51. Nat Neurosci. 2009 Oct;12(10):1229-37 - PubMed
  52. Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):1098-103 - PubMed
  53. Open Biol. 2020 Jan;10(1):190221 - PubMed
  54. Bioinformatics. 2013 Jan 1;29(1):15-21 - PubMed
  55. Nat Genet. 2019 May;51(5):793-803 - PubMed
  56. JAMA. 2017 Sep 26;318(12):1182-1184 - PubMed
  57. Cell. 2015 Aug 27;162(5):1039-50 - PubMed
  58. Nat Genet. 2018 Jul;50(7):912-919 - PubMed
  59. Sci Transl Med. 2018 Dec 19;10(472): - PubMed
  60. Stem Cell Rev Rep. 2019 Oct;15(5):703-716 - PubMed
  61. J Neurol Neurosurg Psychiatry. 2016 Feb;87(2):212-6 - PubMed
  62. Front Cell Neurosci. 2015 Mar 10;9:70 - PubMed
  63. Nature. 2015 Feb 19;518(7539):355-359 - PubMed
  64. Stem Cells. 2008 Jul;26(7):1663-72 - PubMed
  65. Nat Genet. 2006 Dec;38(12):1446-51 - PubMed
  66. Neuron. 2012 Apr 26;74(2):285-99 - PubMed
  67. Science. 2018 Dec 14;362(6420): - PubMed
  68. Trends Neurosci. 1997 Feb;20(2):84-91 - PubMed
  69. Nature. 2012 Apr 11;485(7398):376-80 - PubMed
  70. PLoS One. 2014 May 15;9(5):e94408 - PubMed
  71. Science. 2015 May 8;348(6235):648-60 - PubMed
  72. Nat Genet. 2018 Apr;50(4):621-629 - PubMed
  73. Sci Rep. 2018 Aug 22;8(1):12565 - PubMed
  74. Science. 2007 Apr 20;316(5823):445-9 - PubMed
  75. J Neurosci. 2007 Nov 14;27(46):12555-64 - PubMed
  76. Nature. 2015 Feb 19;518(7539):331-6 - PubMed
  77. Anat Rec. 1970 Aug;167(4):379-87 - PubMed
  78. Mol Autism. 2017 May 22;8:21 - PubMed
  79. Am J Hum Genet. 2016 Dec 1;99(6):1245-1260 - PubMed
  80. Science. 2019 Nov 29;366(6469):1134-1139 - PubMed
  81. JAMA Psychiatry. 2017 Dec 1;74(12):1242-1250 - PubMed

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