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Impact of the Epigenetically Regulated Hoxa-5 Gene in Neural Differentiation from Human Adipose-Derived Stem Cells.
Hernández, Rosa; Jiménez-Luna, Cristina; Ortiz, Raúl; Setién, Fernando; López, Miguel; Perazzoli, Gloria; Esteller, Manel; Berdasco, María; Prados, Jose; Melguizo, Consolación.
Afiliación
  • Hernández R; Center of Biomedical Research (CIBM), Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, 18100 Granada, Spain.
  • Jiménez-Luna C; Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain.
  • Ortiz R; Center of Biomedical Research (CIBM), Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, 18100 Granada, Spain.
  • Setién F; Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain.
  • López M; Center of Biomedical Research (CIBM), Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, 18100 Granada, Spain.
  • Perazzoli G; Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain.
  • Esteller M; Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain.
  • Berdasco M; Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
  • Prados J; Cancer Epigenetics Group, Cancer and Leukemia Epigenetics and Biology Program (PEBCL), Josep Carreras Leukemia Research Institute (IJC), 08916 Barcelona, Spain.
  • Melguizo C; Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
Biology (Basel) ; 10(8)2021 Aug 19.
Article en En | MEDLINE | ID: mdl-34440035
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Guideline Idioma: En Revista: Biology (Basel) Año: 2021 Tipo del documento: Article País de afiliación: España Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Guideline Idioma: En Revista: Biology (Basel) Año: 2021 Tipo del documento: Article País de afiliación: España Pais de publicación: Suiza