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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Transcriptome of iPSC-derived neuronal cells reveals a module of co-expressed genes consistently associated with autism spectrum disorder

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Griesi-Oliveira, K. [1, 2] ; Fogo, M. S. [1, 2] ; Pinto, B. G. G. [2] ; Alves, A. Y. [2] ; Suzuki, A. M. [1] ; Morales, A. G. [1] ; Ezquina, S. [1] ; Sosa, O. J. [3] ; Sutton, G. J. [4] ; Sunaga-Franze, D. Y. [5] ; Bueno, A. P. [2] ; Seabra, G. [6] ; Sardinha, L. [2] ; Costa, S. S. [1] ; Rosenberg, C. [1] ; Zachi, E. C. [7] ; Sertie, A. L. [2] ; Martins-de-Souza, D. [6, 8, 9] ; Reis, E. M. [10] ; Voineagu, I. [4] ; Passos-Bueno, M. R. [1]
Total Authors: 21
[1] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Sao Paulo - Brazil
[2] Hosp Israelita Albert Einstein, Sao Paulo - Brazil
[3] Univ Sao Paulo, Programa Interunidades Posgrad Bioinformat, Sao Paulo - Brazil
[4] Univ New South Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW - Australia
[5] Helmholtz Assoc, Max Delbruck Ctr Mol Med, Berlin - Germany
[6] Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, Lab Neuroprote, Sao Paulo - Brazil
[7] Univ Sao Paulo, Inst Psicol, Dept Psicol Expt, Nucleo Neurociencias & Comportamento, Sao Paulo - Brazil
[8] Conselho Nacl Desenvolvimento Cient & Tecnol CNPq, Inst Nacl Biomarcadores Neuropsiquiatria INBION, Sao Paulo - Brazil
[9] Univ Estadual Campinas, Expt Med Res Cluster EMC, Campinas - Brazil
[10] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo - Brazil
Total Affiliations: 10
Document type: Journal article
Web of Science Citations: 0

Evaluation of expression profile in autism spectrum disorder (ASD) patients is an important approach to understand possible similar functional consequences that may underlie disease pathophysiology regardless of its genetic heterogeneity. Induced pluripotent stem cell (iPSC)-derived neuronal models have been useful to explore this question, but larger cohorts and different ASD endophenotypes still need to be investigated. Moreover, whether changes seen in this in vitro model reflect previous findings in ASD postmortem brains and how consistent they are across the studies remain underexplored questions. We examined the transcriptome of iPSC-derived neuronal cells from a normocephalic ASD cohort composed mostly of high-functioning individuals and from non-ASD individuals. ASD patients presented expression dysregulation of a module of co-expressed genes involved in protein synthesis in neuronal progenitor cells (NPC), and a module of genes related to synapse/neurotransmission and a module related to translation in neurons. Proteomic analysis in NPC revealed potential molecular links between the modules dysregulated in NPC and in neurons. Remarkably, the comparison of our results to a series of transcriptome studies revealed that the module related to synapse has been consistently found as upregulated in iPSC-derived neurons-which has an expression profile more closely related to fetal brain-while downregulated in postmortem brain tissue, indicating a reliable association of this network to the disease and suggesting that its dysregulation might occur in different directions across development in ASD individuals. Therefore, the expression pattern of this network might be used as biomarker for ASD and should be experimentally explored as a therapeutic target. (AU)

FAPESP's process: 16/50324-5 - Gene expression analysis on in vitro neuronal models and post-mortem brain tissues to understand Autism Spectrum Disorder
Grantee:Andréa Laurato Sertié
Support type: Regular Research Grants
FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
Grantee:Mayana Zatz
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 14/10068-4 - Multi-User Equipment approved in grant 13/08711-3: mass spectrometer waters SYNAPT G2-Si HDMS + nanoACQUITY UPLC
Grantee:Daniel Martins-de-Souza
Support type: Multi-user Equipment Program