Wnt3a regulates survival, expansion, and maintenance of neural progenitors derived from human embryonic stem cells.
Many reports describe the efficient derivation and expansion of neural progenitors (NP) from human embryonic stem cells (hESC). However, little is known about the signaling factors found within the neurosphere microenvironment that regulate NP maintenance and differentiation. We show that Wnt ligand and receptor transcripts are endogenously upregulated within neurospheres derived from noggin-primed hESC. In addition, neurosphere formation and size were significantly greater in the presence of exogenous Wnt3a compared to control conditions. Inhibition of endogenous Wnt signaling resulted in a significant reduction in the efficiency of neurosphere formation and overall size, due to effects on both NP proliferation and apoptosis. These findings demonstrate a requirement of Wnt signaling for maintenance, proliferation, and survival of NP when cultured in neurosphere conditions.
Davidson
Kathryn C
KC
Monash Institute of Medical Research, Monash University, The Australian Stem Cell Center, Clayton, Australia.
Jamshidi
Pegah
P
Daly
Rachel
R
Hearn
Milton T W
MT
Pera
Martin F
MF
Dottori
Mirella
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism* / Q000494:pharmacology; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D000099176:Noggin Protein