Davidson Kathryn C, Jamshidi Pegah, Daly Rachel, Hearn Milton T W, Pera Martin F, Dottori Mirella
Monash Institute of Medical Research, Monash University, The Australian Stem Cell Center, Clayton, Australia.
Mol Cell Neurosci. 2007 Nov;36(3):408-15. doi: 10.1016/j.mcn.2007.07.013. Epub 2007 Aug 7.
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.
许多报告描述了从人胚胎干细胞（hESC）高效衍生和扩增神经祖细胞（NP）的方法。然而，对于神经球微环境中调节NP维持和分化的信号因子，我们却知之甚少。我们发现，在由头蛋白预处理的hESC衍生的神经球内，Wnt配体和受体转录本会内源性上调。此外，与对照条件相比，在外源Wnt3a存在的情况下，神经球的形成和大小显著增加。由于对NP增殖和凋亡均有影响，内源性Wnt信号的抑制导致神经球形成效率和总体大小显著降低。这些发现表明，在神经球培养条件下，NP的维持、增殖和存活需要Wnt信号。
