Impact of the Epigenetically Regulated Hoxa-5 Gene in Neural Differentiation from Human Adipose-Derived Stem Cells
Metadatos
Afficher la notice complèteAuteur
Hernández, Rosa; Jiménez Luna, Cristina; Prados Salazar, José Carlos; Ortiz Quesada, Raúl; Perazzoli, Gloria; Melguizo Alonso, ConsolaciónEditorial
MDPI
Materia
Mesenchymal Stem Cells Neuronal differentiation Epigenetic changes Hoxa-5 CRISPR/dCas9
Date
2021Referencia bibliográfica
Hernández, R.; Jiménez-Luna, C.; Ortiz, R.; Setién, F.; López, M.; Perazzoli, G.; Esteller, M.; Berdasco, M.; Prados, J.; Melguizo, C. Impact of the Epigenetically Regulated Hoxa-5 Gene in Neural Differentiation from Human Adipose-Derived Stem Cells. Biology 2021, 10, 802. https://doi.org/ 10.3390/biology10080802
Patrocinador
Fundació La Marató TV3 (111430/31); CTS-107 Group from Junta de AndalucíaRésumé
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.