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Schizophrenia gene regulator identified by study

Using both computational models and stem cell-based experiments, researchers have identified a gene regulator of schizophrenia.

A study has analysed a large collection of brain tissues to identify a gene that acts as a master regulator of schizophrenia in early human brain development. The researchers say that their findings may lay the groundwork for future treatments.

The research was led by the Children’s Hospital of Philadelphia (CHOP), US. The team used computational system approaches to reveal a disease-relevant core pathway in schizophrenia.

Two independent datasets of biological samples from schizophrenia patients and control subjects were analysed by the researchers. Using an algorithm developed at Columbia University, US to reconstruct gene transcription networks, the team identified the gene TCF4 as a regulator of the condition.

Although previous studies have also revealed this gene to be critical in schizophrenia, little is known about its functional effects. The researchers investigated these effects by decreasing the gene’s expression in neural progenitor cells and glutamatergic neurons derived from induced pluripotent stem cells.

When reduced, the TCF4 regulatory networks were enriched for genes involved in neuronal activity, schizophrenia risk genes and schizophrenia-associated de novo mutations.

The researchers say their findings have the potential to be used in further investigations. Their study is one of the first examples of combining computational approaches and stem cell-based experimental models to investigate complex gene networks in psychiatric diseases.

The study was published in Science Advances.

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