title: MicroRNA changes through Müller glia dedifferentiation and early/late rod photoreceptor differentiation.
abstract: Cell-type determination is a complex process driven by the combinatorial effect of extrinsic signals and the expression of transcription factors and regulatory genes. MicroRNAs (miRNAs) are non-coding RNAs that, generally, inhibit the expression of target genes and have been involved, among other processes, in cell identity acquisition. To search for candidate miRNAs putatively involved in mice rod photoreceptor and Müller glia (MG) identity, we compared miRNA expression profiles between late-stage retinal progenitor cells (RPCs), CD73-immunopositive (CD73+) rods and postnatal MG. We found a close similarity between RPCs and CD73+ miRNA expression profiles but a divergence between CD73+ and MG miRNA signatures. We validated preferentially expressed miRNAs in the CD73+ subpopulation (miR-182, 183, 124a, 9(∗), 181c and 301b(∗)) or MG (miR-143, 145, 214, 199a-5p, 199b(∗), and 29a). Taking advantage of the unique capacity of MG to dedifferentiate into progenitor-like cells that can be differentiated to a rod phenotype in response to external cues, we evaluated changes of selected miRNAs in MG-derived progenitors (MGDP) during neuronal differentiation. We found decreased levels of miR-143 and 145, but increased levels of miR-29a in MGDP. In MGDPs committed to early neuronal lineages we found increased levels of miR-124a and upregulation of miR-124a, 9(∗) and 181c during MGDP acquisition of rod phenotypes. Furthermore, we demonstrated that ectopic miR-124 expression is sufficient to enhance early neuronal commitment of MGDP. Our data reveal a dynamic regulation of miRNAs in MGDP through early and late neuronal commitment and miRNAs that could be potential targets to exploit the silent neuronal differentiation capacity of MG in mammals.
authors.affiliation: Departamento de Farmacobiología, CINVESTAV-Sede Sur, México D.F., Mexico.
authors.forename: H
authors.initials: H
authors.lastname: Quintero
authors.affiliation: Departamento de Farmacobiología, CINVESTAV-Sede Sur, México D.F., Mexico.
authors.forename: A I
authors.initials: AI
authors.lastname: Gómez-Montalvo
authors.affiliation: Departamento de Farmacobiología, CINVESTAV-Sede Sur, México D.F., Mexico. Electronic address: mlamas@cinvestav.mx.
authors.forename: M
authors.initials: M
authors.lastname: Lamas
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D063928:Ependymoglial Cells / Q000187:drug effects / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D012160:Retina / Q000166:cytology; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D013234:Stem Cells
chemical_list: D005136:Eye Proteins; D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D015720:5'-Nucleotidase; D005974:Glutamate-Ammonia Ligase
keywords: Müller glia; microRNA; photoreceptor; retina; retinal progenitor cell