Hernández, RosaJiménez-Luna, CristinaOrtiz, RaúlSetién, FernandoLópez, MiguelPerazzoli, GloriaEsteller, ManelBerdasco, MaríaPrados, JoseMelguizo, Consolación2022-09-302022-09-302021-08-19Hernández 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.http://hdl.handle.net/10668/4194Human 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Mesenchymal stem cellsNeuronal differentiationEpigenetic changesHoxa-5CRISPR/ dCas9Células madre mesenquimatosasEpigénesis genéticaProteína 9 asociada a CRISPRMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Base Sequence::Repetitive Sequences, Nucleic Acid::Tandem Repeat Sequences::Inverted Repeat Sequences::Clustered Regularly Interspaced Short Palindromic RepeatsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, EssentialMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, GeneticMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, PharmacologicalMedical Subject Headings::Diseases::Nervous System DiseasesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Cell- and Tissue-Based TherapyMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intercellular Signaling Peptides and Proteins::Nerve Growth Factors::Neuregulinsresearch article34440035Acceso abierto10.3390/biology100808022079-7737PMC8389620