Research Description
Neural pathway of human embryonic stem cells
Our lab focuses on how human neuroepithelial cells are specified and subsequently differentiated into neurons and glia. We approach this question by the use of (human and nonhuman) primate embryonic stem (ES) cells that are generated from the inner cell mass of preimplantation embryos. We have established a culture system to differentiate the ES cells to neuroepithelial cells, which recapitulates the earliest neural development in terms of temporal course and the formation of neural tube-like structures. Using this system, we are dissecting the molecular mechanism of neural induction in humans by assessing the effects of known molecules on human neural specification and identifying unknown genes or those that might be unique to neural induction in humans.
Differentiation of neuroepithelia to neurons and glia is controlled by both cell autonomous and extracellular signals. To decode this information, we will express neural cell type-specific transcriptional factor genes in human ES cells and follow their differentiation course. In parallel, we are creating culture systems to mimic the spatial patterning of in vivo neuroepithelia in response to a morphogen gradient. As such, we will integrate cell intrinsic and extrinsic signals for the production of a specific cell type in terms of time and space. We focus on midbrain dopamine neurons, spinal cord motoneurons, and myelinating oligodendrocytes, all of which use a similar ventralized signal, sonic hedgehog, but different molecules for rostro-caudal or lineage selections. Information gained from these studies will provide the basic principles of human neural cell differentiation, thus enabling us to devise strategies to instigate regeneration in injured or diseased brain. It should also offer a solution to the generation of an enriched population of specialized neural cells for drug screening and cell replacement therapy, our long-term goal.
Recent Publications
Zhang S-C, Wernig M, Duncan ID, Brustle O, Thomson JA (2001): In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nature Biotechnol., 19, 1129-1133.
Zhang S-C (2001): Defining glial cells during CNS development. Nature Rev. Neurosci. 2, 840-843.
Zhang S-C, Ge B, Duncan ID (1999): Adult brain retains the potential to generate oligodendroglial progenitors with extensive myelination capacity. Proc. Natl. Acad. Sci. USA, 96, 4089-4094.
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