Efficient derivation of functional floor plate tissue from human embryonic stem cells Journal Article
| Authors: | Fasano, C. A.; Chambers, S. M.; Lee, G.; Tomishima, M. J.; Studer, L. |
| Article Title: | Efficient derivation of functional floor plate tissue from human embryonic stem cells |
| Abstract: | The floor plate (FP) is a critical signaling center during neural development located along the ventral midline of the embryo. Little is known about human FP development because of the lack of tissue accessibility. Here we report the efficient derivation of human embryonic stem cell (hESC)-derived FP tissue capable of secreting Netrin-1 and SHH and patterning primary and hESC derived tissues. FP induction in hESCs is dependent on early SHH exposure and occurs at the expense of anterior neurectoderm (AN). Global gene expression and functional studies identify SHH-mediated inhibition of Dkk-1 as key factor in FP versus AN specification. hESC-derived FP tissue is shown to be of anterior SIX6+ character but is responsive to caudalizing factors suppressing SIX6 expression and inducing a shift in usage of region-specific SHH enhancers. These data define the early signals that drive human FP versus AN specification and determine regional identity in hESC-derived FP. © 2010 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; intercellular signaling peptides and proteins; unclassified drug; human cell; nonhuman; genetic analysis; forkhead transcription factors; animal cell; mouse; animals; mice; animal tissue; cell cycle; reverse transcription polymerase chain reaction; enzyme inhibition; gene expression; gene expression profiling; embryo; embryonic stem cell; sonic hedgehog protein; hedgehog proteins; nerve tissue proteins; transcription factor; embryo development; cell differentiation; transcription, genetic; in vitro study; time factors; b lymphocyte induced maturation protein 1; cell lineage; gene expression regulation, developmental; quantitative analysis; protein secretion; embryonic stem cells; upregulation; transcriptome; body patterning; protein patched 1; endoderm; nervous system; transcription factor sox17; dickkopf 1 protein; hepatocyte nuclear factor 3beta; netrin 1; transcription factor nkx2.1; transcription factor nkx6.1; transcription factor sox1; neuroectoderm; hepatocyte nuclear factor 3-beta; neural plate |
| Journal Title: | Cell Stem Cell |
| Volume: | 6 |
| Issue: | 4 |
| ISSN: | 1934-5909 |
| Publisher: | Cell Press |
| Date Published: | 2010-04-02 |
| Start Page: | 336 |
| End Page: | 347 |
| Language: | English |
| DOI: | 10.1016/j.stem.2010.03.001 |
| PUBMED: | 20362538 |
| PROVIDER: | scopus |
| PMCID: | PMC4336800 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 5" - "Export Date: 20 April 2011" - "Source: Scopus" |
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