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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Version of Record online: 1 SEP 2009
Copyright © 2009 AlphaMed Press
Volume 27, Issue 12, pages 2906–2916, December 2009
How to Cite
Weick, J. P., Austin Johnson, M. and Zhang, S.-C. (2009), Developmental Regulation of Human Embryonic Stem Cell-Derived Neurons by Calcium Entry via Transient Receptor Potential Channels. STEM CELLS, 27: 2906–2916. doi: 10.1002/stem.212
Author contributions: J.P.W. and M.A.J.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; J.P.W. and M.A.J. contributed equally to this work; S.-C.Z.: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of manuscript.
First published online in STEM CELLS EXPRESS September 1, 2009.
Disclosure of potential conflicts of interest is found at the end of this article.
- Issue online: 14 DEC 2009
- Version of Record online: 1 SEP 2009
- Accepted manuscript online: 1 SEP 2009 12:00AM EST
- Manuscript Accepted: 16 AUG 2009
- Manuscript Received: 29 MAY 2009
- NINDS, NS. Grant Number: 045926
- Waisman Center from the National Institute of Child Health and Human Development. Grant Number: HD03352
- Rath Distinguished Graduate Student Fellowship
- NIH Stem Cell Training Grant. Grant Number: NIH T32AG027566-01
- Voltage-gated calcium channels;
- Embryonic stem cells
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) and postmitotic neurons (PMNs) generated from embryonic stem cells display robust Ca2+ transients. Unlike previous reports in animal models, transients occurred by a Gd3+/La3+-sensitive, but thapsigargin- and Cd2+-insensitive, mechanism, strongly suggestive of a role for transient receptor potential (Trp) channels. Furthermore, Ca2+ transients in PMNs exhibited an additional sensitivity to the canonical Trp (TrpC) antagonist SKF96365 and shRNA-mediated knockdown of the TrpC1 subunit. Functionally, inhibition of Ca2+ transients in dividing hNE cells led to a significant reduction in proliferation, whereas either pharmacological inhibition or shRNA-mediated knockdown of the TrpC1 and TrpC4 subunits significantly reduced neurite extension in PMNs. Primary neurons cultured from fetal human cortex displayed nearly identical Ca2+ transients and pharmacological sensitivities to Trp channel antagonists. Together these data suggest that Trp channels present a novel mechanism for controlling Ca2+ transients in human neurons and may offer a target for regulating proliferation and neurite outgrowth when engineering cells for therapeutic transplantation. STEM CELLS 2009;27:2906–2916