RESUMEN
Recent years have improved our understanding of the plasticity of cell types behind inducing, building, and maintaining different types of teeth. The latest efforts were aided by progress in single-cell transcriptomics, which helped to define not only cell states with mathematical precision but also transitions between them. This includes new aspects of dental epithelial and mesenchymal stem cell niches and beyond. These recent efforts revealed continuous and fluid trajectories connecting cell states during dental development and exposed the natural plasticity of tooth-building progenitors. Such "developmental" plasticity seems to be employed for organizing stem cell niches in adult continuously growing teeth. Furthermore, transitions between mature cell types elicited by trauma might represent a replay of embryonic continuous cell states. Alternatively, they could constitute transitions that evolved de novo, not known from the developmental paradigm. In this review, we discuss and exemplify how dental cell types exhibit plasticity during dynamic processes such as development, self-renewal, repair, and dental replacement. Hypothetically, minor plasticity of cell phenotypes and greater plasticity of transitions between cell subtypes might provide a better response to lifetime challenges, such as damage or dental loss. This plasticity might be additionally harnessed by the evolutionary process during the elaboration of dental cell subtypes in different animal lineages. In turn, the diversification of cell subtypes building teeth brings a diversity of their shape, structural properties, and functions.
Asunto(s)
Diente , Animales , Regeneración/fisiologíaRESUMEN
Childhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. Here we study single-cell and single-nuclei transcriptomes of neuroblastoma with different clinical risk groups and stages, including healthy adrenal gland. We compare tumor cell populations with embryonic mouse sympatho-adrenal derivatives, and post-natal human adrenal gland. We provide evidence that low and high-risk neuroblastoma have different cell identities, representing two disease entities. Low-risk neuroblastoma presents a transcriptome that resembles sympatho- and chromaffin cells, whereas malignant cells enriched in high-risk neuroblastoma resembles a subtype of TRKB+ cholinergic progenitor population identified in human post-natal gland. Analyses of these populations reveal different gene expression programs for worst and better survival in correlation with age at diagnosis. Our findings reveal two cellular identities and a composition of human neuroblastoma tumors reflecting clinical heterogeneity and outcome.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/genética , Glándulas Suprarrenales/metabolismo , Glicoproteínas de Membrana/genética , Proteínas de Neoplasias/genética , Neuroblastoma/genética , Receptor trkB/genética , Transcriptoma , Neoplasias de las Glándulas Suprarrenales/metabolismo , Neoplasias de las Glándulas Suprarrenales/mortalidad , Neoplasias de las Glándulas Suprarrenales/patología , Glándulas Suprarrenales/patología , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Diferenciación Celular , Núcleo Celular/genética , Núcleo Celular/metabolismo , Preescolar , Células Cromafines/metabolismo , Células Cromafines/patología , Diagnóstico Precoz , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Lactante , Masculino , Glicoproteínas de Membrana/metabolismo , Ratones , Proteínas de Neoplasias/clasificación , Proteínas de Neoplasias/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/mortalidad , Neuroblastoma/patología , Receptor trkB/metabolismo , Medición de Riesgo , Análisis de la Célula Individual , Especificidad de la Especie , Análisis de SupervivenciaRESUMEN
In organized tissues, the precise geometry and the overall shape are critical for the specialized functions that the cells carry out. Odontoblasts are major matrix-producing cells of the tooth and have also been suggested to participate in sensory transmission. However, refined morphologic data on these important cells are limited, which hampers the analysis and understanding of their cellular functions. We took advantage of fluorescent color-coding genetic tracing to visualize and reconstruct in 3 dimensions single odontoblasts, pulp cells, and their assemblages. Our results show distinct structural features and compartments of odontoblasts at different stages of maturation, with regard to overall cellular shape, formation of the main process, orientation, and matrix deposition. We demonstrate previously unanticipated contacts between the processes of pulp cells and odontoblasts. All reported data are related to mouse incisor tooth. We also show that odontoblasts express TRPM5 and Piezo2 ion channels. Piezo2 is expressed ubiquitously, while TRPM5 is asymmetrically distributed with distinct localization to regions proximal to and within odontoblast processes.
Asunto(s)
Imagenología Tridimensional/métodos , Odontoblastos/citología , Ameloblastos/citología , Ameloblastos/ultraestructura , Animales , Compartimento Celular , Núcleo Celular/ultraestructura , Forma de la Célula , Extensiones de la Superficie Celular/ultraestructura , Pulpa Dental/citología , Pulpa Dental/ultraestructura , Dentina/ultraestructura , Matriz Extracelular/ultraestructura , Técnica del Anticuerpo Fluorescente , Incisivo/citología , Incisivo/ultraestructura , Canales Iónicos/ultraestructura , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/ultraestructura , Ratones , Ratones Transgénicos , Microscopía Electrónica de Rastreo/métodos , Odontoblastos/ultraestructura , Canales Catiónicos TRPM/ultraestructuraRESUMEN
Cell migration is essential for the development of numerous structures derived from embryonic neural crest cells (NCCs), however the underlying molecular mechanisms are incompletely understood. NCCs migrate long distances in the embryo and contribute to many different cell types, including peripheral neurons, glia and pigment cells. In the present work we report expression of Nedd9, a scaffolding protein within the integrin signaling pathway, in non-lineage-restricted neural crest progenitor cells. In particular, Nedd9 was found to be expressed in the dorsal neural tube at the time of neural crest delamination and in early migrating NCCs. To analyze the role of Nedd9 in neural crest development we performed loss- and gain-of-function experiments and examined the subsequent effects on delamination and migration in vitro and in vivo. Our results demonstrate that loss of Nedd9 activity in chick NCCs perturbs cell spreading and the density of focal complexes and actin filaments, properties known to depend on integrins. Moreover, a siRNA dose-dependent decrease in Nedd9 activity results in a graded reduction of NCC's migratory distance while forced overexpression increases it. Retinoic acid (RA) was found to regulate Nedd9 expression in NCCs. Our results demonstrate in vivo that Nedd9 promotes the migration of NCCs in a graded manner and suggest a role for RA in the control of Nedd9 expression levels.