cAMP initiates early phase neuron-like morphology changes and late phase neural differentiation in mesenchymal stem cells
- 20 August 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cellular and Molecular Life Sciences
- Vol. 68 (5), 863-876
- https://doi.org/10.1007/s00018-010-0497-1
Abstract
The intracellular second messenger cAMP is frequently used in induction media to induce mesenchymal stem cells (MSCs) into neural lineage cells. To date, an understanding of the role cAMP exerts on MSCs and whether cAMP can induce MSCs into functional neurons is still lacking. We found cAMP initiated neuron-like morphology changes early and neural differentiation much later. The early phase changes in morphology were due to cell shrinkage, which subsequently rendered some cells apoptotic. While the morphology changes occurred prior to the expression of neural markers, it is not required for neural marker expression and the two processes are differentially regulated downstream of cAMP-activated protein kinase A. cAMP enabled MSCs to gain neural marker expressions with neuronal function, such as, calcium rise in response to neuronal activators, dopamine, glutamate, and potassium chloride. However, only some of the cells induced by cAMP responded to the three neuronal activators and further lack the neuronal morphology, suggesting that although cAMP is able to direct MSCs towards neural differentiation, they do not achieve terminal differentiation.Keywords
This publication has 61 references indexed in Scilit:
- Isolation and Enrichment of Rat Mesenchymal Stem Cells (MSCs) and Separation of Single-colony Derived MSCsJournal of Visualized Experiments, 2010
- Geometric cues for directing the differentiation of mesenchymal stem cellsProceedings of the National Academy of Sciences of the United States of America, 2010
- Voltage-gated potassium channels as therapeutic targetsNature Reviews Drug Discovery, 2009
- cAMP/PKA Regulates Osteogenesis, Adipogenesis and Ratio of RANKL/OPG mRNA Expression in Mesenchymal Stem Cells by Suppressing LeptinPLOS ONE, 2008
- Involvement of astroglial ceramide in palmitic acid‐induced Alzheimer‐like changes in primary neuronsEuropean Journal of Neuroscience, 2007
- Compartmentalized Phosphorylation of IAP by Protein Kinase A Regulates CytoprotectionMolecular Cell, 2007
- Neural differentiation of mesenchymal-like stem cells from cord blood is mediated by PKABiochemical and Biophysical Research Communications, 2007
- Insights into the mechanism of microtubule stabilization by TaxolProceedings of the National Academy of Sciences, 2006
- Molecular pathways involved in neural in vitro differentiation of marrow stromal stem cellsJournal of Cellular Biochemistry, 2004
- Transcriptional regulation by the phosphorylation-dependent factor CREBNature Reviews Molecular Cell Biology, 2001