Adipose stromal cells are promising tools for clinical applications in regeneration therapies, due to their ease of isolation from tissue and its high yield; however, their ability to transdifferentiate into neural phenotypes is still a matter of controversy. Here, we show that combined chemical and neurotrophin stimulation resulted in neuron-like morphology and regulated expression and activity of several genes involved in neurogenesis and neurotransmission as well as ion currents mediated by NMDA and GABA receptors. Among them, expression patterns of genes coding for kinin-B1 and B2, α7 nicotinic, M1, M3 and M4 muscarinic acetylcholine, glutamatergic (AMPA2 and mGlu2), purinergic P2Y1 and P2Y4 and GABAergic (GABA-A, β3-subunit) receptors and neuronal nitric oxide synthase were up-regulated compared to levels of undifferentiated cells. Simultaneously, expression levels of P2X1, P2X4, P2X7 and P2Y6 purinergic and M5 muscarinic acetylcholine receptors were down-regulated. Agonist-induced activity levels of the studied receptor classes also augmented during neuronal transdifferentiation. Transdifferentiated cells expressed high levels of neuronal β3-tubulin, NF-H, NeuN and MAP-2 proteins as well as increased ASCL1, MYT1 and POU3F2 gene expression known to drive neuronal fate determination. The presented work contributes to a better understanding of transdifferentiation induced by neurotrophins for a prospective broad spectrum of medical applications.
Keywords: Adipose stromal cells; Human lipoaspirate; Mesenchymal stem cells; Neuronal differentiation; Transdifferentiation.
P19 embryonal carcinoma cells as in vitro model for studying purinergic receptor expression and modulation of N-methyl-D-aspartate-glutamate and acetylcholine receptors during neuronal differentiation.Neuroscience. 2007 May 25;146(3):1169-81. doi: 10.1016/j.neuroscience.2007.02.041. Epub 2007 Apr 5. Neuroscience. 2007. PMID: 17418494
Kinin-B2 receptor activity determines the differentiation fate of neural stem cells.J Biol Chem. 2012 Dec 28;287(53):44046-61. doi: 10.1074/jbc.M112.407197. Epub 2012 Nov 6. J Biol Chem. 2012. PMID: 23132855 Free PMC article.
P2X4 receptor as a modulator in the function of P2X receptor in CD4+ T cells from peripheral blood and adipose tissue.Mol Immunol. 2019 Aug;112:369-377. doi: 10.1016/j.molimm.2019.06.009. Epub 2019 Jul 3. Mol Immunol. 2019. PMID: 31279218
Molecular pharmacology of P2Y-receptors.Naunyn Schmiedebergs Arch Pharmacol. 2000 Nov;362(4-5):310-23. doi: 10.1007/s002100000310. Naunyn Schmiedebergs Arch Pharmacol. 2000. PMID: 11111826 Review.
Neurotransmitter receptor expression and activity during neuronal differentiation of embryonal carcinoma and stem cells: from basic research towards clinical applications.Cell Prolif. 2006 Aug;39(4):281-300. doi: 10.1111/j.1365-2184.2006.00385.x. Cell Prolif. 2006. PMID: 16872363 Free PMC article. Review.