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First published online April 10, 2009
doi: 10.1242/10.1242/dev.029447

Development 136, 1443-1452 (2009)
Published by The Company of Biologists 2009
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Human oligodendrocytes from embryonic stem cells: conserved SHH signaling networks and divergent FGF effects

Bao-Yang Hu*, Zhong-Wei Du*, Xue-Jun Li, Melvin Ayala and Su-Chun Zhang{dagger}

Departments of Anatomy and Neurology, School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, WI 53705, USA.

{dagger} Author for correspondence (e-mail: zhang{at}waisman.wisc.edu)

Accepted 23 February 2009

Human embryonic stem cells (hESCs) offer a platform to bridge what we have learned from animal studies to human biology. Using oligodendrocyte differentiation as a model system, we show that sonic hedgehog (SHH)-dependent sequential activation of the transcription factors OLIG2, NKX2.2 and SOX10 is required for sequential specification of ventral spinal OLIG2-expressing progenitors, pre-oligodendrocyte precursor cells (pre-OPCs) and OPCs from hESC-derived neuroepithelia, indicating that a conserved transcriptional network underlies OPC specification in human as in other vertebrates. However, the transition from pre-OPCs to OPCs is protracted. FGF2, which promotes mouse OPC generation, inhibits the transition of pre-OPCs to OPCs by repressing SHH-dependent co-expression of OLIG2 and NKX2.2. Thus, despite the conservation of a similar transcriptional network across vertebrates, human stem/progenitor cells may respond differently to those of other vertebrates to certain extrinsic factors.

Key words: Glia, Myelination, Neuron-glial switch, Purmorphamine, Transplantation


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Related articles in Development:

Oligodendrocyte differentiation: human ES cells take it slow

Development 2009 136: e901. [Full Text]  





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