Transcriptome Analysis of iPSC-Derived Neurons from Rubinstein-Taybi Patients Reveals Deficits in Neuronal Differentiation.
Animals
Biomarkers
/ metabolism
Case-Control Studies
Cell Differentiation
/ genetics
Cell Line
Cerebral Cortex
/ pathology
Gene Expression Profiling
Gene Expression Regulation
Gene Ontology
Humans
Induced Pluripotent Stem Cells
/ metabolism
Mice
Models, Biological
Neurons
/ metabolism
Rubinstein-Taybi Syndrome
/ genetics
Tissue Donors
Defective transcriptional program
Intellectual disability
Neuronal differentiation
RNA-Seq
Rubinstein Taybi
iNeurons
iPSC-derived neural progenitors
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
09
03
2020
accepted:
08
06
2020
pubmed:
21
6
2020
medline:
4
6
2021
entrez:
21
6
2020
Statut:
ppublish
Résumé
Rubinstein-Taybi syndrome (RSTS) is a rare multisystem developmental disorder with moderate to severe intellectual disability caused by heterozygous mutations of either CREBBP or EP300 genes encoding CBP/p300 chromatin regulators. We explored the gene programs and processes underlying the morphological and functional alterations shown by iPSC-derived neurons modeling RSTS to bridge the molecular changes resulting from defective CBP/p300 to cognitive impairment. By global transcriptome analysis, we compared the differentially expressed genes (DEGs) marking the transition from iPSC-derived neural progenitors to cortical neurons (iNeurons) of five RSTS patients carrying private CREBBP/EP300 mutations and manifesting differently graded neurocognitive signs with those of four healthy controls. Our data shows a defective and altered neuroprogenitor to neuron transcriptional program in the cells from RSTS patients. First, transcriptional regulation is weaker in RSTS as less genes than in controls are modulated, including genes of key processes of mature functional neurons, such as those for voltage-gated channels and neurotransmitters and their receptors. Second, regulation is subverted as genes acting at pre-terminal stages of neural differentiation in cell polarity and adhesive functions (members of the cadherin family) and axon extension/guidance (members of the semaphorins and SLIT receptors families) are improperly upregulated. Impairment or delay of RSTS neuronal differentiation program is also evidenced by decreased modulation of the overall number of neural differentiation markers, significantly impacting the initial and final stages of the differentiation cascade. Last, extensive downregulation of genes for RNA/DNA metabolic processes confirms that RSTS is a global transcription disorder, consistent with a syndrome driven by chromatin dysregulation. Interestingly, the morphological and functional alterations we have previously appointed as biomarkers of RSTS iNeurons provide functional support to the herein designed transcriptome profile pointing to key dysregulated neuronal genes as main contributors to patients' cognitive deficit. The impact of RSTS transcriptome may go beyond RSTS as comparison of dysregulated genes across modeled neurodevelopmental disorders could unveil convergent genes of cognitive impairment.
Identifiants
pubmed: 32562237
doi: 10.1007/s12035-020-01983-6
pii: 10.1007/s12035-020-01983-6
pmc: PMC7399686
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3685-3701Subventions
Organisme : Ministero della Salute
ID : ERA-Net Neuron JTC2015
Organisme : Ministero della Salute
ID : RC08C921
Références
Hennekam RC (2006) Rubinstein-Taybi syndrome. Eur J Hum Genet 14:981–985. https://doi.org/10.1038/sj.ejhg.5201594
doi: 10.1038/sj.ejhg.5201594
pubmed: 16868563
Spena S, Milani D, Rusconi D, Negri G, Colapietro P, Elcioglu N, Bedeschi F, Pilotta A et al (2015) Insights into genotype-phenotype correlations from CREBBP point mutation screening in a cohort of 46 Rubinstein-Taybi syndrome patients. Clin Genet 88:431–440. https://doi.org/10.1111/cge.12537
doi: 10.1111/cge.12537
pubmed: 25388907
Fergelot P, Van Belzen M, Van Gils J, Afenjar A, Armour CM, Arveiler B, Beets L, Burglen L et al (2016) Phenotype and genotype in 52 patients with Rubinstein-Taybi syndrome caused by EP300 mutations. Am J Med Genet A 170:3069–3082. https://doi.org/10.1002/ajmg.a.37940
doi: 10.1002/ajmg.a.37940
pubmed: 27648933
Negri G, Magini P, Milani D, Colapietro P, Rusconi D, Scarano E, Bonati MT, Priolo M et al (2016) From whole gene deletion to point mutations of EP300-positive Rubinstein-Taybi patients: new insights into the mutational spectrum and peculiar clinical hallmarks. Hum Mutat 37:175–183. https://doi.org/10.1002/humu.22922
doi: 10.1002/humu.22922
pubmed: 26486927
Bjornsson HT (2015) The Mendelian disorders of the epigenetic machinery. Genome Res 25:1473–1481. https://doi.org/10.1101/gr.190629.115
doi: 10.1101/gr.190629.115
pubmed: 26430157
pmcid: 4579332
Dancy BM, Cole PA (2015) Protein lysine acetylation by p300/CBP. Chem Rev 115:2419–2452. https://doi.org/10.1021/cr500452k
doi: 10.1021/cr500452k
pubmed: 25594381
pmcid: 4378506
Fahrner JA, Bjornsson HT (2019) Mendelian disorders of the epigenetic machinery: postnatal malleability and therapeutic prospects. Hum Mol Genet 28:R254–R264. https://doi.org/10.1093/hmg/ddz174
doi: 10.1093/hmg/ddz174
pubmed: 31595951
Lipinski M, Del Blanco B, Barco A (2019) CBP/p300 in brain development and plasticity: disentangling the KAT’s cradle. Curr Opin Neurobiol 59:1–8. https://doi.org/10.1016/j.conb.2019.01.023
doi: 10.1016/j.conb.2019.01.023
pubmed: 30856481
Sheikh BN, Akhtar A (2019) The many lives of KATs - detectors, integrators and modulators of the cellular environment. Nat Rev Genet 20:7–23. https://doi.org/10.1038/s41576-018-0072-4
doi: 10.1038/s41576-018-0072-4
pubmed: 30390049
Ajmone PF, Avignone S, Gervasini C, Giacobbe A, Monti F, Costantino A, Esposito S, Marchisio P et al (2018) Rubinstein-Taybi syndrome: new neuroradiological and neuropsychiatric insights from a multidisciplinary approach. Am J Med Genet B Neuropsychiatr Genet 177:406–415. https://doi.org/10.1002/ajmg.b.32628
doi: 10.1002/ajmg.b.32628
pubmed: 29637745
Alarcon JM, Malleret G, Touzani K, Vronskaya S, Ishii S, Kandel ER, Barco A (2004) Chromatin acetylation, memory, and LTP are impaired in CBP+/- mice: a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. Neuron 42:947–959. https://doi.org/10.1016/j.neuron.2004.05.021
doi: 10.1016/j.neuron.2004.05.021
pubmed: 15207239
Korzus E, Rosenfeld MG, Mayford M (2004) CBP histone acetyltransferase activity is a critical component of memory consolidation. Neuron 42:961–972. https://doi.org/10.1016/j.neuron.2004.06.002
doi: 10.1016/j.neuron.2004.06.002
pubmed: 15207240
Valor LM, Viosca J, Lopez-Atalaya JP, Barco A (2013) Lysine acetyltransferases CBP and p300 as therapeutic targets in cognitive and neurodegenerative disorders. Curr Pharm Des 19:5051–5064. https://doi.org/10.2174/13816128113199990382
doi: 10.2174/13816128113199990382
pubmed: 23448461
pmcid: 3722569
Medrano-Fernandez A, Delgado-Garcia JM, Del Blanco B, Llinares M, Sanchez-Campusano R, Olivares R, Gruart A, Barco A (2019) The epigenetic factor CBP is required for the differentiation and function of medial ganglionic eminence-derived interneurons. Mol Neurobiol 56:4440–4454. https://doi.org/10.1007/s12035-018-1382-4
doi: 10.1007/s12035-018-1382-4
pubmed: 30334186
Tsui D, Voronova A, Gallagher D, Kaplan DR, Miller FD, Wang J (2014) CBP regulates the differentiation of interneurons from ventral forebrain neural precursors during murine development. Dev Biol 385:230–241. https://doi.org/10.1016/j.ydbio.2013.11.005
doi: 10.1016/j.ydbio.2013.11.005
pubmed: 24247009
Wang J, Weaver IC, Gauthier-Fisher A, Wang H, He L, Yeomans J, Wondisford F, Kaplan DR et al (2010) CBP histone acetyltransferase activity regulates embryonic neural differentiation in the normal and Rubinstein-Taybi syndrome brain. Dev Cell 18:114–125. https://doi.org/10.1016/j.devcel.2009.10.023
doi: 10.1016/j.devcel.2009.10.023
pubmed: 20152182
Del Blanco B, Guiretti D, Tomasoni R, Lopez-Cascales MT, Munoz-Viana R, Lipinski M, Scandaglia M, Coca Y et al (2019) CBP and SRF co-regulate dendritic growth and synaptic maturation. Cell Death Differ 26:2208–2222. https://doi.org/10.1038/s41418-019-0285-x
doi: 10.1038/s41418-019-0285-x
pubmed: 30850733
pmcid: 6889142
Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, Hanna J, Lodato MA et al (2010) Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A 107:21931–21936. https://doi.org/10.1073/pnas.1016071107
doi: 10.1073/pnas.1016071107
pubmed: 21106759
pmcid: 3003124
Weinert BT, Narita T, Satpathy S, Srinivasan B, Hansen BK, Scholz C, Hamilton WB, Zucconi BE et al (2018) Time-resolved analysis reveals rapid dynamics and broad scope of the CBP/p300 acetylome. Cell 174:231–244 e212. https://doi.org/10.1016/j.cell.2018.04.033
doi: 10.1016/j.cell.2018.04.033
pubmed: 29804834
pmcid: 6078418
Bedford DC, Kasper LH, Fukuyama T, Brindle PK (2010) Target gene context influences the transcriptional requirement for the KAT3 family of CBP and p300 histone acetyltransferases. Epigenetics 5:9–15. https://doi.org/10.4161/epi.5.1.10449
doi: 10.4161/epi.5.1.10449
pubmed: 20110770
pmcid: 2829352
Lopez-Atalaya JP, Gervasini C, Mottadelli F, Spena S, Piccione M, Scarano G, Selicorni A, Barco A et al (2012) Histone acetylation deficits in lymphoblastoid cell lines from patients with Rubinstein-Taybi syndrome. J Med Genet 49:66–74. https://doi.org/10.1136/jmedgenet-2011-100354
doi: 10.1136/jmedgenet-2011-100354
pubmed: 21984751
Alari V, Russo S, Rovina D, Garzo M, Crippa M, Calzari L, Scalera C, Concolino D et al (2019) Generation of three iPSC lines (IAIi002, IAIi004, IAIi003) from Rubinstein-Taybi syndrome 1 patients carrying CREBBP non sense c.4435G>T, p.(Gly1479*) and c.3474G>A, p.(Trp1158*) and missense c.4627G>T, p.(Asp1543Tyr) mutations. Stem Cell Res 40:101553. https://doi.org/10.1016/j.scr.2019.101553
doi: 10.1016/j.scr.2019.101553
pubmed: 31491690
Alari V, Russo S, Rovina D, Gowran A, Garzo M, Crippa M, Mazzanti L, Scalera C et al (2018) Generation of the Rubinstein-Taybi syndrome type 2 patient-derived induced pluripotent stem cell line (IAIi001-A) carrying the EP300 exon 23 stop mutation c.3829A>T, p.(Lys1277*). Stem Cell Res 30:175–179. https://doi.org/10.1016/j.scr.2018.06.009
doi: 10.1016/j.scr.2018.06.009
pubmed: 29944992
Alari V, Russo S, Terragni B, Ajmone PF, Sironi A, Catusi I, Calzari L, Concolino D et al (2018) iPSC-derived neurons of CREBBP- and EP300-mutated Rubinstein-Taybi syndrome patients show morphological alterations and hypoexcitability. Stem Cell Res 30:130–140. https://doi.org/10.1016/j.scr.2018.05.019
doi: 10.1016/j.scr.2018.05.019
pubmed: 29883886
Lin M, Lachman HM, Zheng D (2016) Transcriptomics analysis of iPSC-derived neurons and modeling of neuropsychiatric disorders. Mol Cell Neurosci 73:32–42. https://doi.org/10.1016/j.mcn.2015.11.009
doi: 10.1016/j.mcn.2015.11.009
pubmed: 26631648
DeRosa BA, El Hokayem J, Artimovich E, Garcia-Serje C, Phillips AW, Van Booven D, Nestor JE, Wang L et al (2018) Convergent pathways in idiopathic autism revealed by time course transcriptomic analysis of patient-derived neurons. Sci Rep 8:8423. https://doi.org/10.1038/s41598-018-26495-1
doi: 10.1038/s41598-018-26495-1
pubmed: 29849033
pmcid: 5976773
Wang P, Lin M, Pedrosa E, Hrabovsky A, Zhang Z, Guo W, Lachman HM, Zheng D (2015) CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in neurodevelopment. Mol Autism 6:55. https://doi.org/10.1186/s13229-015-0048-6
doi: 10.1186/s13229-015-0048-6
pubmed: 26491539
pmcid: 4612430
Cheung AY, Horvath LM, Grafodatskaya D, Pasceri P, Weksberg R, Hotta A, Carrel L, Ellis J (2011) Isolation of MECP2-null Rett syndrome patient hiPS cells and isogenic controls through X-chromosome inactivation. Hum Mol Genet 20:2103–2115. https://doi.org/10.1093/hmg/ddr093
doi: 10.1093/hmg/ddr093
pubmed: 21372149
pmcid: 3090191
Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y, Chen G, Gage FH et al (2010) A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143:527–539. https://doi.org/10.1016/j.cell.2010.10.016
doi: 10.1016/j.cell.2010.10.016
pubmed: 21074045
pmcid: 3003590
Boland MJ, Nazor KL, Tran HT, Szucs A, Lynch CL, Paredes R, Tassone F, Sanna PP et al (2017) Molecular analyses of neurogenic defects in a human pluripotent stem cell model of fragile X syndrome. Brain 140:582–598. https://doi.org/10.1093/brain/aww357
doi: 10.1093/brain/aww357
pubmed: 28137726
pmcid: 5837342
Halevy T, Czech C, Benvenisty N (2015) Molecular mechanisms regulating the defects in fragile X syndrome neurons derived from human pluripotent stem cells. Stem Cell Rep 4:37–46. https://doi.org/10.1016/j.stemcr.2014.10.015
doi: 10.1016/j.stemcr.2014.10.015
Germain ND, Chen PF, Plocik AM, Glatt-Deeley H, Brown J, Fink JJ, Bolduc KA, Robinson TM et al (2014) Gene expression analysis of human induced pluripotent stem cell-derived neurons carrying copy number variants of chromosome 15q11-q13.1. Mol Autism 5:44. https://doi.org/10.1186/2040-2392-5-44
doi: 10.1186/2040-2392-5-44
pubmed: 25694803
pmcid: 4332023
Nagy J, Kobolak J, Berzsenyi S, Abraham Z, Avci HX, Bock I, Bekes Z, Hodoscsek B et al (2017) Altered neurite morphology and cholinergic function of induced pluripotent stem cell-derived neurons from a patient with Kleefstra syndrome and autism. Transl Psychiatry 7:e1179. https://doi.org/10.1038/tp.2017.144
doi: 10.1038/tp.2017.144
pubmed: 28742076
pmcid: 5538124
Zhao X, Bhattacharyya A (2018) Human models are needed for studying human neurodevelopmental disorders. Am J Hum Genet 103:829–857. https://doi.org/10.1016/j.ajhg.2018.10.009
doi: 10.1016/j.ajhg.2018.10.009
pubmed: 30526865
pmcid: 6288051
Sharma N, Jadhav SP, Bapat SA (2010) CREBBP re-arrangements affect protein function and lead to aberrant neuronal differentiation. Differentiation 79:218–231. https://doi.org/10.1016/j.diff.2010.02.001
doi: 10.1016/j.diff.2010.02.001
pubmed: 20207472
Iwase S, Berube NG, Zhou Z, Kasri NN, Battaglioli E, Scandaglia M, Barco A (2017) Epigenetic etiology of intellectual disability. J Neurosci 37:10773–10782. https://doi.org/10.1523/JNEUROSCI.1840-17.2017
doi: 10.1523/JNEUROSCI.1840-17.2017
pubmed: 29118205
pmcid: 5678009
Larizza L, Finelli P (2019) Developmental disorders with intellectual disability driven by chromatin dysregulation: clinical overlaps and molecular mechanisms. Clin Genet 95:231–240. https://doi.org/10.1111/cge.13365
doi: 10.1111/cge.13365
pubmed: 29672823
Bentivegna A, Milani D, Gervasini C, Castronovo P, Mottadelli F, Manzini S, Colapietro P, Giordano L et al (2006) Rubinstein-Taybi syndrome: spectrum of CREBBP mutations in Italian patients. BMC Med Genet 7:77. https://doi.org/10.1186/1471-2350-7-77
doi: 10.1186/1471-2350-7-77
pubmed: 17052327
pmcid: 1626071
Negri G, Milani D, Colapietro P, Forzano F, Della Monica M, Rusconi D, Consonni L, Caffi LG et al (2015) Clinical and molecular characterization of Rubinstein-Taybi syndrome patients carrying distinct novel mutations of the EP300 gene. Clin Genet 87:148–154. https://doi.org/10.1111/cge.12348
doi: 10.1111/cge.12348
pubmed: 24476420
Supek F, Bosnjak M, Skunca N, Smuc T (2011) REVIGO summarizes and visualizes long lists of gene ontology terms. PLoS One 6:e21800. https://doi.org/10.1371/journal.pone.0021800
doi: 10.1371/journal.pone.0021800
pubmed: 21789182
pmcid: 3138752
Koropouli E, Kolodkin AL (2014) Semaphorins and the dynamic regulation of synapse assembly, refinement, and function. Curr Opin Neurobiol 27:1–7. https://doi.org/10.1016/j.conb.2014.02.005
doi: 10.1016/j.conb.2014.02.005
pubmed: 24598309
Um JW, Kim KH, Park BS, Choi Y, Kim D, Kim CY, Kim SJ, Kim M et al (2014) Structural basis for LAR-RPTP/Slitrk complex-mediated synaptic adhesion. Nat Commun 5:5423. https://doi.org/10.1038/ncomms6423
doi: 10.1038/ncomms6423
pubmed: 25394468
Elizalde C, Campa VM, Caro M, Schlangen K, Aransay AM, Vivanco M, Kypta RM (2011) Distinct roles for Wnt-4 and Wnt-11 during retinoic acid-induced neuronal differentiation. Stem Cells 29:141–153. https://doi.org/10.1002/stem.562
doi: 10.1002/stem.562
pubmed: 21280163
Habib N, Li Y, Heidenreich M, Swiech L, Avraham-Davidi I, Trombetta JJ, Hession C, Zhang F et al (2016) Div-Seq: single-nucleus RNA-Seq reveals dynamics of rare adult newborn neurons. Science 353:925–928. https://doi.org/10.1126/science.aad7038
doi: 10.1126/science.aad7038
pubmed: 27471252
pmcid: 5480621
Zeisel A, Munoz-Manchado AB, Codeluppi S, Lonnerberg P, La Manno G, Jureus A, Marques S, Munguba H et al (2015) Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science 347:1138–1142. https://doi.org/10.1126/science.aaa1934
doi: 10.1126/science.aaa1934
Farioli-Vecchioli S, Saraulli D, Costanzi M, Leonardi L, Cina I, Micheli L, Nutini M, Longone P et al (2009) Impaired terminal differentiation of hippocampal granule neurons and defective contextual memory in PC3/Tis21 knockout mice. PLoS One 4:e8339. https://doi.org/10.1371/journal.pone.0008339
doi: 10.1371/journal.pone.0008339
pubmed: 20020054
pmcid: 2791842
Burk K, Ramachandran B, Ahmed S, Hurtado-Zavala JI, Awasthi A, Benito E, Faram R, Ahmad H et al (2018) Regulation of dendritic spine morphology in hippocampal neurons by Copine-6. Cereb Cortex 28:1087–1104. https://doi.org/10.1093/cercor/bhx009
doi: 10.1093/cercor/bhx009
pubmed: 28158493
Grosse G, Draguhn A, Hohne L, Tapp R, Veh RW, Ahnert-Hilger G (2000) Expression of Kv1 potassium channels in mouse hippocampal primary cultures: development and activity-dependent regulation. J Neurosci 20:1869–1882
doi: 10.1523/JNEUROSCI.20-05-01869.2000
Lopez-Atalaya JP, Valor LM, Barco A (2014) Epigenetic factors in intellectual disability: the Rubinstein-Taybi syndrome as a paradigm of neurodevelopmental disorder with epigenetic origin. Prog Mol Biol Transl Sci 128:139–176. https://doi.org/10.1016/B978-0-12-800977-2.00006-1
doi: 10.1016/B978-0-12-800977-2.00006-1
pubmed: 25410544
Hu BY, Weick JP, Yu J, Ma LX, Zhang XQ, Thomson JA, Zhang SC (2010) Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc Natl Acad Sci U S A 107:4335–4340. https://doi.org/10.1073/pnas.0910012107
doi: 10.1073/pnas.0910012107
pubmed: 20160098
pmcid: 2840097
Meyer K, Feldman HM, Lu T, Drake D, Lim ET, Ling KH, Bishop NA, Pan Y et al (2019) REST and neural gene network dysregulation in iPSC models of Alzheimer’s disease. Cell Rep 26:1112–1127 e1119. https://doi.org/10.1016/j.celrep.2019.01.023
doi: 10.1016/j.celrep.2019.01.023
pubmed: 30699343
pmcid: 6386196
Amiri A, Coppola G, Scuderi S, Wu F, Roychowdhury T, Liu F, Pochareddy S, Shin Y et al (2018) Transcriptome and epigenome landscape of human cortical development modeled in organoids. Science 362. https://doi.org/10.1126/science.aat6720
Basu R, Taylor MR, Williams ME (2015) The classic cadherins in synaptic specificity. Cell Adhes Migr 9:193–201. https://doi.org/10.1080/19336918.2014.1000072
doi: 10.1080/19336918.2014.1000072
Tran TS, Rubio ME, Clem RL, Johnson D, Case L, Tessier-Lavigne M, Huganir RL, Ginty DD et al (2009) Secreted semaphorins control spine distribution and morphogenesis in the postnatal CNS. Nature 462:1065–1069. https://doi.org/10.1038/nature08628
doi: 10.1038/nature08628
pubmed: 20010807
pmcid: 2842559
Won SY, Lee P, Kim HM (2019) Synaptic organizer: Slitrks and type IIa receptor protein tyrosine phosphatases. Curr Opin Struct Biol 54:95–103. https://doi.org/10.1016/j.sbi.2019.01.010
doi: 10.1016/j.sbi.2019.01.010
pubmed: 30822649
Fink JJ, Levine ES (2018) Uncovering true cellular phenotypes: using induced pluripotent stem cell-derived neurons to study early insults in neurodevelopmental disorders. Front Neurol 9:237. https://doi.org/10.3389/fneur.2018.00237
doi: 10.3389/fneur.2018.00237
pubmed: 29713304
pmcid: 5911479
Mariani J, Coppola G, Zhang P, Abyzov A, Provini L, Tomasini L, Amenduni M, Szekely A et al (2015) FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders. Cell 162:375–390. https://doi.org/10.1016/j.cell.2015.06.034
doi: 10.1016/j.cell.2015.06.034
pubmed: 26186191
pmcid: 4519016
Wang P, Mokhtari R, Pedrosa E, Kirschenbaum M, Bayrak C, Zheng D, Lachman HM (2017) CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in cerebral organoids derived from iPS cells. Mol Autism 8:11. https://doi.org/10.1186/s13229-017-0124-1
doi: 10.1186/s13229-017-0124-1
pubmed: 28321286
pmcid: 5357816
Mills JA, Herrera PS, Kaur M, Leo L, McEldrew D, Tintos-Hernandez JA, Rajagopalan R, Gagne A et al (2018) NIPBL(+/−) haploinsufficiency reveals a constellation of transcriptome disruptions in the pluripotent and cardiac states. Sci Rep 8:1056. https://doi.org/10.1038/s41598-018-19173-9
doi: 10.1038/s41598-018-19173-9
pubmed: 29348408
pmcid: 5773608
Soares FA, Pedersen RA, Vallier L (2016) Generation of human induced pluripotent stem cells from peripheral blood mononuclear cells using Sendai virus. Methods Mol Biol 1357:23–31. https://doi.org/10.1007/7651_2015_202
doi: 10.1007/7651_2015_202
pubmed: 25687300
Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M et al (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29:15–21. https://doi.org/10.1093/bioinformatics/bts635
doi: 10.1093/bioinformatics/bts635
pubmed: 23104886
pmcid: 23104886
Liao Y, Smyth GK, Shi W (2014) featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30:923–930. https://doi.org/10.1093/bioinformatics/btt656
doi: 10.1093/bioinformatics/btt656
pubmed: 24227677
Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550. https://doi.org/10.1186/s13059-014-0550-8
doi: 10.1186/s13059-014-0550-8
pubmed: 25516281
pmcid: 25516281
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504. https://doi.org/10.1101/gr.1239303
doi: 10.1101/gr.1239303
pubmed: 14597658
pmcid: 14597658
Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, Fridman WH, Pages F et al (2009) ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25:1091–1093. https://doi.org/10.1093/bioinformatics/btp101
doi: 10.1093/bioinformatics/btp101
pubmed: 19237447
pmcid: 2666812