Modeling psychiatric disorders in a dish
Schizophrenia is a complex polygenic disorder that arises from a summation of many common genetic variants that ultimately equate to genetic predisposition. In addition, genetic heterogeneity further enhances the complexity of causation. For these reasons, it is very difficult to model Schizophrenia in the laboratory using traditional cell and animal models because it is difficult to engineer all of the common variants into a model. To overcome this obstacle, the Stem Cell Biology group is creating cell models directly from Schizophrenia patients; thereby all of the common variants that each individual genome contains are fully represented in the model.
The Stem Cell Biology group is reprogramming patient fibroblasts into induced pluripotent stem (iPS) cells. These iPS cells are capable of producing any cell of the body including brain cells. LIBD scientists are currently differentiating these iPS cells into neural stem cells and cortical neurons to identify differences in their biology compared to iPS cells produced from control individuals. Ultimately, biological differences between patients and controls will become the targets for development of therapeutic interventions with the goal of normalizing the observed difference.
Modeling psychiatry in a dish. (A) The upper panel shows a confocal image of human neurons stained with a nuclear marker (DAPI, blue) and a marker that labels filaments within the neurites (Map2, green). The lower panel shows a differential interference contrast image of a field of living human neurons. In the lower left corner, a glass electrode is recording electrical activity from a single neuron. (B) Examples electrophysiology traces depicting the electrical properties of human neurons. Upper traces show spontaneous synaptic transmission. Middle traces show evoked action potential trains. Lower traces show activation of voltage-gated ion channels.