Combining Patient-Reprogrammed Neural Cells and Proteomics as a Model to Study Psychiatric Disorders
The mechanisms underlying the pathophysiology of psychiatric disorders are still poorly known. Most of the studies about these disorders have been conducted on postmortem tissue or in limited preclinical models. The development of human induced pluripotent stem cells (iPSCs) has helped to increase the translational capacity of molecular profiling studies of psychiatric disorders through provision of human neuronal-like tissue. This approach consists of generation of pluripotent cells by genetically reprogramming somatic cells to produce the multiple neural cell types as observed within the nervous tissue. The finding that iPSCs can recapitulate the phenotype of the donor also affords the possibility of using this approach to study both the disease and control states in a given medical area. Here, we present a protocol for differentiation of human pluripotent stem cells to neural progenitor cells followed by subcellular fractionation which allows the study of specific cellular organelles and proteomic analysis.
KeywordsPsychiatric disorders Brain iPSC Neuronal precursor cell Differentiation Proteomics Mass spectrometry
GSZ, DMS, and JMN are supported by the São Paulo Research Foundation (FAPESP) grants 16/04912-2, 13/08711-3, and 14/21035-0.
- 1.Martins-de-Souza D, Solari FA, Guest PC, Zahedi RP, Steiner J (2015) Biological pathways modulated by antipsychotics in the blood plasma of schizophrenia patients and their association to a clinical response. NPJ Schizophrenia 1:15050. doi: 10.1038/npjschz.2015.50 CrossRefPubMedPubMedCentralGoogle Scholar