Laboratory of Stem cell Differentiation

Our research is focused on the derivation of functional neurons from various cell sources including human pluripotent stem (hPS) cells. One main application of our laboratory is the utilization of human ES or iPS cell-derived neurons for the development of cell replacement therapy to cure neurodegeneration disease, especially Parkinson’s disease (PD). Secondly, we also direct our research interests to utilize normal and disease-specific pluripotent stem cell lines for studying the function of genes involved in human brain development and in the pathology of neurodegeneration disease.

Midbrain Dopamine Neurons

Our previous study generated a novel floor plate-based strategy for the derivation of human dopamine (DA) neurons that efficiently engraft in vivo. Midbrain floor plate precursors are differentiated from hPSCs by exposure to small molecule activators of SHH and canonical WNT signaling. Engraftable midbrain DA neurons are obtained and can be maintained in vitro for several months. Extensive molecular profiling, biochemical and electrophysiological data define developmental progression and confirm the identity of hPSC-derived midbrain DA neurons. Excellent DA neuron survival, function, and lack of neural overgrowth in the animal models indicate promise for the development of cell-based therapies in PD.

Hindbrain Serotonin Neurons and Organoids

Serotonin neurons, the major components of the raphe nuclei, arise from ventral hindbrain progenitors. We established a novel strategy to generate hindbrain serotonin neurons from hPSCs, which involves the formation of ventral-type neural progenitor cells and stimulation of the hindbrain serotonin neural development. A caudalizing agent, retinoid acid (RA), is used to direct the cells into the hindbrain cell fate. hPSCs successfully develop into serotonin-expressing neurons using our protocol. Additionally, our monolayer differentiation system can be further modified to generate serotonin neuron-enriched hindbrain-like organoids. Our methodology may become a powerful tool for future studies related to serotonin neurotransmission.