Generation of functional neurons from adult human mucosal olfactory ensheathing glia by direct lineage conversion

• Published in: Cell death & disease 2024-07, Vol.15 (7), p.478-11, Article 478
• Main Authors: Portela-Lomba, María, Simón, Diana, Callejo-Móstoles, Marta, de la Fuente, Gemma, Fernández de Sevilla, David, García-Escudero, Vega, Moreno-Flores, M. Teresa, Sierra, Javier
• Format: Article
• Language: English
• Subjects: 13; 13/1; 13/100; 13/109; 13/44; 13/51; 14/19; 14/63; 631/378/1687; 692/308/2171; Adult; Animals; Antibodies; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Beta2 protein; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Culture; Cell Lineage; Cells, Cultured; Central nervous system; Engraftment; Glutamatergic transmission; Hippocampus - cytology; Hippocampus - metabolism; Humans; Immunology; Life Sciences; Mice; Mucosa; Nervous system; Neurogenesis; Neuroglia - cytology; Neuroglia - metabolism; Neuronal-glial interactions; Neurons - cytology; Neurons - metabolism; Olfactory Bulb - cytology; Olfactory Bulb - metabolism; Olfactory Mucosa - cytology; Olfactory Mucosa - metabolism; Regeneration; Somatic cells; Transcription factors; γ-Aminobutyric acid
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-024-06862-9

A recent approach to promote central nervous system (CNS) regeneration after injury or disease is direct conversion of somatic cells to neurons. This is achieved by transduction of viral vectors that express neurogenic transcription factors. In this work we propose adult human mucosal olfactory ensheathing glia (hmOEG) as a candidate for direct reprogramming to neurons due to its accessibility and to its well-characterized neuroregenerative capacity. After induction of hmOEG with the single neurogenic transcription factor NEUROD1, the cells under study exhibited morphological and immunolabeling neuronal features, fired action potentials and expressed glutamatergic and GABAergic markers. In addition, after engraftment of transduced hmOEG cells in the mouse hippocampus, these cells showed specific neuronal labeling. Thereby, if we add to the neuroregenerative capacity of hmOEG cultures the conversion to neurons of a fraction of their population through reprogramming techniques, the engraftment of hmOEG and hmOEG-induced neurons could be a procedure to enhance neural repair after central nervous system injury.