Developmental Regulation of Human Embryonic Stem Cell‐Derived Neurons by Calcium Entry via Transient Receptor Potential Channels
作者： Jason P. Weick , M. Austin Johnson , Su-Chun Zhang
DOI: 10.1002/STEM.212
关键词:
摘要: Spontaneous calcium (Ca2+) transients in the developing nervous system can affect proliferation, migration, neuronal subtype specification, and neurite outgrowth. Here, we show that telencephalic human neuroepithelia (hNE) postmitotic neurons (PMNs) generated from embryonic stem cells display robust Ca2+ transients. Unlike previous reports animal models, occurred by a Gd3+/La3+-sensitive, but thapsigargin- Cd2+-insensitive, mechanism, strongly suggestive of role for transient receptor potential (Trp) channels. Furthermore, PMNs exhibited an additional sensitivity to canonical Trp (TrpC) antagonist SKF96365 shRNA-mediated knockdown TrpC1 subunit. Functionally, inhibition dividing hNE led significant reduction whereas either pharmacological or TrpC4 subunits significantly reduced extension PMNs. Primary cultured fetal cortex displayed nearly identical sensitivities channel antagonists. Together these data suggest channels present novel mechanism controlling may offer target regulating proliferation outgrowth when engineering therapeutic transplantation. STEM CELLS 2009;27:2906–2916
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