Bioengineered Human Neural Organoids

Despite its importance in central nervous system development, development of the human nervous system remains poorly understood.

We have developed the first completely patterned human neural tube model by engineering morphogen environments of human pluripotent stem cells. This neural tube model recaptulates key development landmarks, including the formation of a single continuous central lumen enclosed by neuronal progenitor cells, nested expression of HOX genes along rostral-caudal axis, patterned expression of canonical dorsal-ventral regional markers, and emergence of isthmic organizer, neural crest cells, and neuromesodermal progenitors.

In addition to these technical breakthroughs, we have also revealed new biological insights in human neural development, including the pre-patterning of axial identities of neural crest cells and functional roles of neuromesodermal progenitors in trunk neural crest development.

In the future, we are interested in the following research directions:
  • Develop next-generation neural organoids with improved interregional interactions and functional neural circuits.
  • Study the etiology of neural developmental disorders such as autism spectrum disease and brain malformation by integrating spatially organized neural organoids with patient iPSCs, CRISPR screening and single cell sequencing.
  • Decipher the molecular mechanism underlying the regional patterning of neural crest cells and craniofacial abnormalities.
  • Develop region-specific neural tube folding model using hPSCs and study the roles of genetic and environmental factors in human neural tube defects including anencephaly and spina bifida.