Su-Chun Zhang

 

 

Embryonic Stem Cells and Neural Differentiation

E-mail: zhang@waisman.wisc.edu

Research Strength: Development: Plasticity and Repair

Our laboratory intends to answer how functionally diversified neuronal and glial subtypes are born in the making of our human brain and how stem/progenitor cells may be diverted to needed functional neurons and glia for repairing the injured/diseased brain. We have developed models of neural differentiation from mouse, monkey, and human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) that recapitulate key events occurring during early embryo development, including induction of multipotential neuroepithelial cells that form neural tube-like structures, patterning of region-specific neural progenitors, and generation of neurons and glia with particular transmitter or functional phenotypes. In parallel, we are building transgenic human stem cell lines with regulatable gene expression. Together, we are dissecting biochemical interactions underlying the cellular differentiation processes under defined conditions. Such studies will hopefully bridge what we have learned from animal studies to human biology.

By introducing disease-provoking genes into ESCs or by activating the pluoripotent state of genetically mutated adult cells, we are creating model systems in which pathological cellular and molecular processes may be analyzed in bona fide human neurons and glia in a simplified environment. Such systems may be transformed to templates for pharmaceutical screening.

The specialized neural cells produced from normal human ESCs or iPSCs in our laboratory are being tested for their therapeutic potential in animal models of neurological diseases such as Parkinson’s disease, amyotrophic lateral sclerosis, spinal cord injury, and multiple sclerosis. In parallel, we are aiming at promoting regeneration from endogenous neural stem/progenitor cells by utilizing the information gained from studies of neural specification from stem cells and reprogramming of adult cells. Our long-term goal is to translate stem cell technology to the re-building of our injured or diseased brain.

Website:

http://www.waisman.wisc.edu/faculty/zhang.html

Lab Website:

http://www.waisman.wisc.edu/scrp/zhang.html

Selected Publications:

• Xi, J., S.C. Zhang. 2008. Stem cells in development of therapeutics for Parkinson’s disease. J.Cell. Biochem. 105:1153-60.
• Xia, X., M. Ayala, B.R. Thiede, S.C. Zhang. 2008. In Vitro and In Vivo Induced Transgene Expression in Human Embryonic Stem Cells and Derivatives. Stem Cells 26: 525-533. [PDF]
• Yang, D., Z. Zhang, M. Oldenburg, M. Ayala, S.C.Zhang. 2008. Human ES cell-derived dopamine neurons reverse functional deficit in a Parkinson’s rat. Stem Cells 26: 55-63. [PDF]
• Pankratz, M.T., X.J. Li, T.M. Lavaute, E.A. Lyons, X. Chen, S.C. Zhang. 2007. Directed neural differentiation of human embryonic stem cells via an obligated primitive anterior stage. Stem Cells 25: 1511-1520. [PDF]
• Johnson, M.A., J. Weick, R. Pearce, S.C. Zhang. 2007. Functional neural development of human embryonic stem cells: Accelerated synaptic activity via astrocyte co-culture. J. Neurosci. 27:3069-3077. [PDF]
• Krencik, R., and S.C. Zhang. 2006. Stem cell neural differentiation: a model for chemical biology. Current Opinion in Chemical Biology 10: 592-597. [PDF]
• Zhang, S.C. 2006. Neural subtype specification from embryonic stem cells. Brain Pathology 16: 132-142. [PDF]
• Odorico, J., and S.C. Zhang. 2005. In R. Pedersen (ed), Human Embryonic Stem Cells. BIOS Sci Pub.
• Yan, Y., D.L. Yang, E.D. Zarnowska, Z.W. Du, C. Valliere, R.A. Pearce, J.A. Thomson, S.C. Zhang. 2005. Directed differentiation of dopaminergic neuronal subtypes from human embryonic stem cells. Stem Cells 23: 781-790. [PDF]
• Li, X.J., Z.W. Du, E.D. Zarnowska, M. Pankratz, L.O. Hansen, R.A. Pearce, S.C. Zhang. 2005. Specification of motoneurons from human embryonic stem cells. Nat. Biotechnol. 23: 215-221. [PDF]
• Du, Z.W. and S.C. Zhang. 2004. Neural differentiation from embryonic stem cells: Which way? Stem Cell & Dev. 13: 372-381.
• Zhang, S.C. 2003. Embryonic stem cells for neural replacement therapy: Prospects and challenges. J. Hematother. Stem Cell Res. 12: 625-634.
• Zhang, S.C., M. Wernig, I.D. Duncan, O. Brustle, and J.A. Thomson. 2001. In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat. Biotechnol. 19: 1129-1133. [PDF]
• Zhang, S.C. 2001. Defining glial cells during CNS development. Nat. Rev. Neurosci. 2: 840-843. [PDF]
• Zhang, S.C., B. Ge, and I.D. Duncan. 1999. Adult brain retains the potential to generate oligodendroglial progenitors with extensive myelination capacity. Proc. Natl. Acad. Sci. 96: 4089-4094. [PDF]