| Abstract | Experimental measurements indicate a second signal mechanism, in addition to canonical WNT signaling, being involved in the regulation of nuclear B-catenin levels during the cell fate commitment phase of neural differentiation. |
| Author Summary | However, to control hNPC differentiation within the scope of stem cell engineering, a thorough understanding of cell fate determination and its endogenous regulation is required. |
| Author Summary | Here we investigate the spatio-temporal regulation of WNT/fi-catenin signaling in the process of cell fate commitment in hNPCs, which has been reported to play a crucial role for the differentiation process of hNPCs. |
| Conclusion and Outlook | In a combined in-vitro and in-silico approach we find strong evidence, that cell fate commitment in human neural progenitor cells is driven by two distinct fi-catenin signaling mechanisms. |
| Introduction | However, controlling NPC differentiation in stem cell engineering demands a thorough understanding of neuronal and glial cell fate determination and its endogenous regulation. |
| Introduction | A first characterization of ReNcell VM197 hNPC cell fate commitment uncovered a spa-tio-temporal regulation of WNT/fi-catenin key proteins, like LRP6, DVL, AXIN and fi-catenin throughout the entire phase of early differentiation [8]. |
| Introduction | However, the exact mechanisms that drive the WNT/fi-catenin signaling and therewith control the cell fate commitment in hNPC remain unclear. |
| Nuclear ,B-catenin dynamics during early differentiation in human neural progenitor cells | We evaluate the impact of lipid raft disruption on WNT/fi-catenin signaling during differentiation by measuring the temporal progress of WNT signaling in terms of nuclear fi-catenin concentrations in methyl-fi-cyclodextrin-treated and untreated cells in the process of cell fate commitment. |
| Results/Discussion | To explore the potential mechanisms that drive the spatio-temporal regulation of fi-catenin signaling during cell fate commitment and to close this important gap in existing models, we built a comprehensive, stochastic WNT/fi-catenin signaling model, that combines both, mem-brane-related and intracellular processes. |
| transcription signal. | This allows us to study WNT signaling in the context of cell fate commitment in a time dependent manner. |