Neural stem cell biology
Our long-standing question is how neural stem cells are regulated to achieve precise cell division, cell migration, cell fate specification, and differentiation. We focus on understanding the regulation of neural stem cells during neuronal development and in the adult brain using both mouse and human induced pluripotent stem cell (iPSC) models.
Whereas transcriptional regulation of stem cells has been intensively studied, very little is known about how post-transcriptional mechanisms may modulate stem cell properties. Especially, recent evidence suggests that various chemical modifications on RNA can affect mRNA metabolism including decay, transport, splicing, and translation, leading to the emergence of the field of epitranscriptomics. Similar to epigenetic modification, dynamic and reversible epitranscriptomic modification on RNA allows further flexibility on the regulation of gene expression in various tissues. We endeavor to decipher the molecular mechanisms controlling RNA metabolism in neural stem cells during normal development and how alterations in RNA regulatory programs lead to human brain disorders.
Modeling human neurodevelopmental disorders with 3D brain organoid
Using the remarkable self-organizing capability of stem cells, the small human-brain-like structure can be created in a dish.
3D organoids for various regions of the brain provide an unprecedented opportunity to investigate the complex features of human brain development and disease. With patient-derived iPSC and gene-edited pluripotent stem cells mimicking patient mutations by CRISPR/Cas9 technology, we study the etiology and pathology of human neurodevelopmental disorders, such as microcephaly, autism, and schizophrenia, in 3D brain organoid models.