We have generated a new tool to study brain function on the cellular level. The differentiation of pluripotent stem cells like embryonic or induced pluripotent stem cells into functional nerve cells (neurons) remains a challenge. We here demonstrated that specific factors that normally regulate brain development can be exploited to “fast forward” the differentiation of human stem cells into neurons. Since these neurons are induced using exogenous factors we call these cells “induced neuronal cells” or in brief “iN” cells. Stem cell-derived iN cells show all principal functional properties of neurons, ie, they can communicate with each other (form synapses) and use electrical signals to convey information (ability to generate action potentials). Within just 2-3 weeks fully functional neuronal networks can be established using these human neurons.
We next demonstrated that different factor combinations yields different kind of neurons allowing us to reconstruct complex cell mixtures resembling those of normal neuronal cultures.
We also show that iN cells are useful proxies that report disease traits on the cellular level. In particular we demonstrated that a gene mutation that is associated with Schizophrenia leads to a functional defect measurable in human iN cells. This might lead to important new methods to find treatments for these devastating diseases.