Impact of the epigenetically regulated hoxa-5 gene in neural differentiation from human adipose-derived stem cells
Hernández, R. (Universidad de Granada)
Jiménez-Luna, Cristina (Universidad de Granada)
Ortiz, Raúl (Universidad de Granada. Departamento de Anatomía y Embriología)
Setién, Fernando (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
López, Miguel (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Perazzoli, Gloria (Universidad de Granada)
Esteller, M (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Berdasco, Maria (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Prados, José (Universidad de Granada. Departamento de Anatomía y Embriología)
Melguizo, Consolación (Universidad de Granada. Departamento de Anatomía y Embriología)

Date:	2021
Abstract:	Human adipose-derived mesenchymal stem cells (hASCs) may be used in some nervous system pathologies, although obtaining an adequate degree of neuronal differentiation is an important barrier to their applicability. This requires a deep understanding of the expression and epigenetic changes of the most important genes involved in their differentiation. We used hASCs from human lipoaspirates to induce neuronal-like cells through three protocols (Neu1, 2, and 3), determined the degree of neuronal differentiation using specific biomarkers in culture cells and neurospheres, and analyzed epigenetic changes of genes involved in this differentiation. Furthermore, we selected the Hoxa-5 gene to determine its potential to improve neuronal differentiation. Our results showed that an excellent hASC neuronal differentiation process using Neu1 which efficiently modulated NES, CHAT, SNAP25, or SCN9A neuronal marker expression. In addition, epigenetic studies showed relevant changes in Hoxa-5, GRM4, FGFR1, RTEL1, METRN, and PAX9 genes. Functional studies of the Hoxa-5 gene using CRISPR/dCas9 and lentiviral systems showed that its overexpression induced hASCs neuronal differentiation that was accelerated with the exposure to Neu1. These results suggest that Hoxa-5 is an essential gene in hASCs neuronal differentiation and therefore, a potential candidate for the development of cell therapy strategies in neurological disorders.
Note:	Altres ajuts: La Marató de TV3 (111430/31); Junta de Andalucía (CTS-107 Group)
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Mesenchymal stem cells ; Neuronal differentiation ; Epigenetic changes ; Hoxa-5 ; CRISPR/dCas9
Published in:	Biology, Vol. 10 Núm. 8 (august 2021) , p. 802, ISSN 2079-7737

DOI: 10.3390/biology10080802
PMID: 34440035

17 p, 19.5 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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