RT Journal Article
T1 Impact of the Epigenetically Regulated Hoxa-5 Gene in Neural Differentiation from Human Adipose-Derived Stem Cells
A1 Hernández, Rosa
A1 Jiménez-Luna, Cristina
A1 Ortiz, Raúl
A1 Setién, Fernando
A1 López, Miguel
A1 Perazzoli, Gloria
A1 Esteller, Manel
A1 Berdasco, María
A1 Prados, Jose
A1 Melguizo, Consolación
K1 Mesenchymal stem cells
K1 Neuronal differentiation
K1 Epigenetic changes
K1 Hoxa-5
K1 CRISPR/ dCas9
K1 Células madre mesenquimatosas
K1 Epigénesis genética
K1 Proteína 9 asociada a CRISPR
AB 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.
PB MDPI
YR 2021
FD 2021-08-19
LK http://hdl.handle.net/10668/4194
UL http://hdl.handle.net/10668/4194
LA en
NO Hernández R, Jiménez-Luna C, Ortiz R, Setién F, López M, Perazzoli G, et al. Impact of the Epigenetically Regulated Hoxa-5 Gene in Neural Differentiation from Human Adipose-Derived Stem Cells. Biology. 2021 Aug 19;10(8):802.
DS RISalud
RD Apr 8, 2025