Neurogenic differentiation of human adipose-derived stem cells: Relevance of different signaling molecules,transcription factors,and key marker genes |
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Authors: | Alejandra Johana Cardozo,Daniel Eduardo Gó mez,Pablo Francisco Argibay |
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Affiliation: | 1. Instituto de Ciencias Básicas y Medicina Experimental, Hospital Italiano de Buenos Aires, Potosí 4240, Ciudad Autónoma de Buenos Aires (1199), Argentina;2. Laboratorio de Oncología Molecular, Universidad Nacional de Quilmes, R. S. Peña 352, Bernal (1876), Buenos Aires, Argentina |
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Abstract: | Since numerous diseases affect the central nervous system and it has limited self-repair capability, a great interest in using stem cells as an alternative cell source is generated. Previous reports have shown the differentiation of adipose-derived stem cells in neuron-like cells and it has also been proved that the expression pattern of patterning, proneural, and neural factors, such as Pax6, Mash1, Ngn2, NeuroD1, Tbr2 and Tbr1, regulates and defines adult neurogenesis. Regarding this, we hypothesize that a functional parallelism between adult neurogenesis and neuronal differentiation of human adipose-derived stem cells exists. In this study we differentiate human adipose-derived stem cells into neuron-like cells and analyze the expression pattern of different patterning, proneural, neural and neurotransmitter genes, before and after neuronal differentiation. The neuron-like cells expressed neuronal markers, patterning and proneural factors characteristics of intermediate stages of neuronal differentiation. Thus we demonstrated that it is possible to differentiate adipose-derived stem cells in vitro into immature neuron-like cells and that this process is regulated in a similar way to adult neurogenesis. This may contribute to elucidate molecular mechanisms involved in neuronal differentiation of adult human non-neural cells, in aid of the development of potential therapeutic tools for diseases of the nervous system. |
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Keywords: | ASCs, adipose-derived stem cells bHLH, basic Helix&ndash Loop&ndash Helix Mash, mammalian achaete-scute homolog 1 Math, mammalian atonal homolog 1 Ngn, neurogenin NeuroD, neurogenic differentiation Tbr, T-box brain Pax6, paired box gene 6 BHA, butylated hydroxyanisole RA, retinoic acid EGF, epidermal growth factor bFGF, basic fibroblast growth factor CP, crossing point DCX, doublecortin GFAP, glial fibrillary acidic protein MAP2, microtubule-associated protein 2 NSE, neuron specific enolase NF200, neurofilament 200 kDa M1, cholinergic muscarinic receptor 1 GABA, gamma-aminobutyric acid GABRA1, GABA receptor type A subunit α1 GABAbR1, GABA receptor type B subunit 1 GABAbR2, GABA receptor type B subunit 2 GABRD, GABA receptor type A subunit δ NKCC1, Na+, K+, 2Cl&minus co-transporter 1 KCC2, K+/Cl&minus co-transporter 2 GluK5, glutamatergic receptors type kainate subtype 5 mGluR5, metabotropic glutamate receptor 5 NMDA, N-methyl-d-aspartic acid NR1, NMDA 1 receptor |
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