Efficient Derivation of Functional Floor Plate Tissue from Human Embryonic Stem Cells

Christopher A. Fasano, Stuart M. Chambers, Gabsang Lee, Mark J. Tomishima, Lorenz Studer

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)336-347
Number of pages12
JournalCell Stem Cell
Volume6
Issue number4
DOIs
StatePublished - Apr 2 2010
Externally publishedYes

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Human Embryonic Stem Cells
Embryonic Structures
Gene Expression
netrin-1

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Efficient Derivation of Functional Floor Plate Tissue from Human Embryonic Stem Cells. / Fasano, Christopher A.; Chambers, Stuart M.; Lee, Gabsang; Tomishima, Mark J.; Studer, Lorenz.

In: Cell Stem Cell, Vol. 6, No. 4, 02.04.2010, p. 336-347.

Research output: Contribution to journalArticle

Fasano, Christopher A. ; Chambers, Stuart M. ; Lee, Gabsang ; Tomishima, Mark J. ; Studer, Lorenz. / Efficient Derivation of Functional Floor Plate Tissue from Human Embryonic Stem Cells. In: Cell Stem Cell. 2010 ; Vol. 6, No. 4. pp. 336-347.
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