Title: Transcriptome of iPSC-derived neuronal cells reveals a module of co-expressed genes consistently associated with autism spectrum disorder
Author: Cassoli, Juliana S.; Brandão-teles, Caroline; Santana, Aline G.; Souza, Gustavo H. M. F.; De-souza, Daniel Martins
Is part of: PROTEOMICS, v. 17, p. 1700209 -
Citation: Cassoli, Juliana S.; Brandão-teles, Caroline; Santana, Aline G.; Souza, Gustavo H. M. F.; De-souza, Daniel Martins; Transcriptome of iPSC-derived neuronal cells reveals a module of co-expressed genes consistently associated with autism spectrum disorder. PROTEOMICS, v.17, p. 1700209-, 2017
Abstract: 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.
Funding: This work was funded by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP - CEGH/CEPID - 2013/08028-1; SPRINT 2016/50324-5; EMU 2014/10068-4) and by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, 466651/2014-7 and 448536/2014-5). We would like to thank Ms. Renato Davi Puga and Dr. Tatiana Ferreira de Almeida for all the support for bioinformatic analysis and troubleshooting; Ms. Joelcimar Martins da Silva and Dr. Carlos Frederico Menck from CEFAP facility (Instituto de Ciencias Biomedicas -Universidade de Sao Paulo) for the support with imaging acquisition in InCell Analyzer microscope; the statistical support from Nucleo de Apoio ao Pesquisador (Hospital Israelita Albert Einstein); and Dr. Estevao Vadasz for patients' recruitment.