Noggin elicits retinal fate in Xenopus animal cap embryonic stem cells.
Driving specific differentiation pathways in multipotent stem cells is a main goal of cell therapy. Here we exploited the differentiating potential of Xenopus animal cap embryonic stem (ACES) cells to investigate the factors necessary to drive multipotent stem cells toward retinal fates. ACES cells are multipotent, and can be diverged from their default ectodermal fate to give rise to cell types from all three germ layers. We found that a single secreted molecule, Noggin, is sufficient to elicit retinal fates in ACES cells. Reverse-transcription polymerase chain reaction, immunohistochemistry, and in situ hybridization experiments showed that high doses of Noggin are able to support the expression of terminal differentiation markers of the neural retina in ACES cells in vitro. Following in vivo transplantation, ACES cells expressing high Noggin doses form eyes, both in the presumptive eye field region and in ectopic posterior locations. The eyes originating from the transplants in the eye field region are functionally equivalent to normal eyes, as seen by electrophysiology and c-fos expression in response to light. Our data show that in Xenopus embryos, proper doses of a single molecule, Noggin, can drive ACES cells toward retinal cell differentiation without additional cues. This makes Xenopus ACES cells a suitable model system to direct differentiation of stem cells toward retinal fates and encourages further studies on the role of Noggin in the retinal differentiation of mammalian stem cells.
Lan
Lei
L
Dipartimento di Biologia, Università degli Studi di Pisa, Pisa, Italy.
Vitobello
Antonio
A
Bertacchi
Michele
M
Cremisi
Federico
F
Vignali
Robert
R
Andreazzoli
Massimiliano
M
Demontis
Gian Carlo
GC
Barsacchi
Giuseppina
G
Casarosa
Simona
S
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D012160:Retina / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism; D000099176:Noggin Protein
D002352:Carrier Proteins; D029867:Xenopus Proteins; D000099176:Noggin Protein