Researchers at the RIKEN Brain Science Institute have used human-induced pluripotent stem cells (hiPSCs) to identify a characteristic of abnormal brain development in schizophrenia.
Published in Translational Psychiatry, the study shows how deletion of a specific gene known to be associated with schizophrenia leads to abnormal differentiation of neurons and an imbalance between the number of neurons and astrocytes in the brain.
While many genetic factors contribute to schizophrenia, small deletions of a region on chromosome 22 are thought to pose a particular risk because several genes at that location are involved in the development and function of neurons in the brain. To investigate exactly how brain development is altered in schizophrenia by genetic deletions in this region, the team led by Takeo Yoshikawa took advantage of modern stem-cell technology. The researchers produced hiPSCs from people without schizophrenia and from patients with schizophrenia who had this deletion, and compared how the different hiPSCs developed into neurons.
Explains Yoshikawa, “When we analyzed the hiPSCs, we found that patient-derived cells differentiated into fewer neurons and greater numbers of astrocytes. We then went further to determine the molecular mechanism underlying these changes in neurogenic and gliogenic competences.”
Yoshikawa cautions that the molecular mechanisms discovered here may not apply to all cases of schizophrenia. "Our iPS cells from schizophrenia patients are perhaps a special case, because they included the genomic deletion from chromosome 22, which, through MAPK14, led to the imbalance in neuron/astrocyte development. However, there are likely other ways for the same type of imbalance to form in more general cases of schizophrenia."
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