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Diabetes ; 62(10): 3514-22, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23630303

RESUMEN

Knowledge of human pancreas development underpins our interpretation and exploitation of human pluripotent stem cell (PSC) differentiation toward a ß-cell fate. However, almost no information exists on the early events of human pancreatic specification in the distal foregut, bud formation, and early development. Here, we have studied the expression profiles of key lineage-specific markers to understand differentiation and morphogenetic events during human pancreas development. The notochord was adjacent to the dorsal foregut endoderm during the fourth week of development before pancreatic duodenal homeobox-1 detection. In contrast to the published data from mouse embryos, during human pancreas development, we detected only a single-phase of Neurogenin 3 (NEUROG3) expression and endocrine differentiation from approximately 8 weeks, before which Nirenberg and Kim homeobox 2.2 (NKX2.2) was not observed in the pancreatic progenitor cell population. In addition to revealing a number of disparities in timing between human and mouse development, these data, directly assembled from human tissue, allow combinations of transcription factors to define sequential stages and differentiating pancreatic cell types. The data are anticipated to provide a useful reference point for stem cell researchers looking to differentiate human PSCs in vitro toward the pancreatic ß-cell so as to model human development or enable drug discovery and potential cell therapy.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Diferenciación Celular , Proteínas de Homeodominio/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Páncreas/embriología , Páncreas/crecimiento & desarrollo , Factores de Transcripción/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Linaje de la Célula , Sistema Endocrino/embriología , Sistema Endocrino/crecimiento & desarrollo , Femenino , Regulación del Desarrollo de la Expresión Génica , Proteína Homeobox Nkx-2.2 , Proteínas de Homeodominio/genética , Humanos , Inmunohistoquímica , Células Secretoras de Insulina , Ratones , Proteínas del Tejido Nervioso/genética , Proteínas Nucleares , Embarazo , Factores de Transcripción/genética , Proteínas de Pez Cebra
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