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 language | English (US) |
|---|---|
| Pages (from-to) | 336-347 |
| Number of pages | 12 |
| Journal | Cell Stem Cell |
| Volume | 6 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2 2010 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Efficient Derivation of Functional Floor Plate Tissue from Human Embryonic Stem Cells
AU - Fasano, Christopher A.
AU - Chambers, Stuart M.
AU - Lee, Gabsang
AU - Tomishima, Mark J.
AU - Studer, Lorenz
PY - 2010/4/2
Y1 - 2010/4/2
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=77949892562&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2010.03.001
DO - 10.1016/j.stem.2010.03.001
M3 - Article
C2 - 20362538
AN - SCOPUS:77949892562
VL - 6
SP - 336
EP - 347
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 4
ER -