RESUMEN
MicroRNAs post-transcriptionally regulate the expression of approximately 60% of the mammalian genes, and have an important role in maintaining the differentiated state of somatic cells through the expression of unique tissuespecific microRNA sets. Likewise, the stemness of pluripotent cells is also sustained by embryonic stem cell-enriched microRNAs, which regulate genes involved in cell cycle, cell signaling and epigenetics, among others. Thus, microRNAs work as modulator molecules that ensure the appropriate expression profile of each cell type. Manipulation of microRNA expression might determine the cell fate. Indeed, microRNA-mediated reprogramming can change the differentiated status of somatic cells towards stemness or, conversely, microRNAs can also transform stem- into differentiated-cells both in vitro and in vivo. In this Review, we outline what is currently known in this field, focusing on the applications of microRNA in tissue engineering.
Asunto(s)
Células Madre Embrionarias/citología , Mamíferos/genética , MicroARNs/genética , Ingeniería de Tejidos/métodos , Animales , Diferenciación Celular , Linaje de la Célula , Reprogramación Celular , Regulación del Desarrollo de la Expresión Génica , Humanos , Mamíferos/embriología , MicroARNs/metabolismo , Especificidad de ÓrganosRESUMEN
We report a 10-year-old boy with syndromic cleft lip and palate (CLP) and neuro-psychomotor developmental delay. Oligoarray comparative genomic hybridization (aCGH) detected an approximately 300 kb interstitial microduplication at 5p15.33 encompassing 5 protein-coding genes, including TERT and CLPTM1L, and two microRNA genes. Our findings suggest that the duplicated segment predisposes for cleft lip with or without cleft palate (CL/P), or any of the other phenotypic features presented by the patient. A gene coding a similar protein (CLPMT1) has been implicated in CLP etiology both through linkage studies and by a translocation disrupting the gene, indicating the possible involvement of CLPTM1L with CL/P. This is the first report of a possible connection between CLPTM1L and CLP.
Asunto(s)
Duplicación Cromosómica , Cromosomas Humanos Par 5/genética , Labio Leporino/genética , Fisura del Paladar/genética , Proteínas de la Membrana/genética , Proteínas de Neoplasias/genética , Niño , Labio Leporino/diagnóstico , Fisura del Paladar/diagnóstico , Hibridación Genómica Comparativa , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/genética , Humanos , Masculino , MicroARNs/genética , Fenotipo , Telomerasa/genéticaRESUMEN
X chromosome inactivation (XCI) is a comprehensively studied phenomenon that helped to highlight the heritable nature of epigenetic modifications. Although it consists of the transcriptional inactivation of a whole X chromosome in females, some genes escape this process and present bi-allelic expression. Using human fibroblasts with skewed inactivation, we determined allele-specific expression of two X-linked genes previously described to escape XCI in rodent/human somatic cell hybrids, MAOA and GYG2, and the pattern of DNA methylation of their 5' end. Results from these complementary methodologies let us to conclude that both genes are subjected to X inactivation in normal human fibroblasts, indicating that hybrid cells are not an adequate system for studying epigenotypes. We emphasize the need of an analysis of XCI in normal human cell lines, helping us to determine more precisely which X-linked genes contribute to differences among genders and to the phenotypes associated with sex chromosomes aneuploidies.
Asunto(s)
Glucosiltransferasas/genética , Monoaminooxidasa/genética , Inactivación del Cromosoma X , Línea Celular , Islas de CpG , Metilación de ADN , Femenino , Fibroblastos , Genotipo , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
X chromosome inactivation (XCI) in human and mice involves XIST/Xist gene expression from the inactive X (Xi) and repression from the active X (Xa). Repression of the XIST/Xist gene on the Xa has been associated with methylation of its 5' region. In mice, Dnmt1 has been shown to be involved in the methylation and transcriptional repression of Xist on Xa. We examined maintenance of XIST gene repression on Xa in HCT116 cell lines knockout for either DNMT1 or DNMT3B and for DNMT1 and DNMT3B simultaneously. Methylation of the XIST promoter and XIST transcriptional repression is sustained in DNMT1-, DNMT3B- and DNMT1/DNMT3B knockout cells. Despite global DNA demethylation, the double knockout cells present only partial demethylation of the XIST promoter, which is not sufficient for gene reactivation. In contrast, global DNA demethylation with 5-aza-2'-deoxycytidine leads to XIST expression. Therefore, in these human cells maintenance of XIST methylation is controlled differently than global genomic methylation and in the absence of both DNMT1 and DNMT3B.
