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Computational Reconstruction of Pancreatic Islets as a Tool for Structural and Functional Analysis
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Una estructura peninsular coordina la diferenciación asincrónica con la morfogénesis para generar islotes
Nadav Sharon1, Raghav Chawla2, Jonas Mueller3
1Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
Cell
|January 22, 2019
Resumen
Los investigadores descubrieron que la morfología de los islotes pancreáticos y la diferenciación celular endocrina están directamente relacionadas. Este hallazgo desafía las creencias existentes y podría avanzar en la generación de islotes in vitro para el tratamiento de la diabetes.
Área de la Ciencia:
- Biología del desarrollo
- Endocrinología
- Biología de las células madre
Sus antecedentes:
- Los islotes pancreáticos de Langerhans son cruciales para la homeostasis de la glucosa.
- La pérdida de las células beta productoras de insulina conduce a la diabetes; el trasplante de islotes es una cura potencial.
- La comprensión del desarrollo de los islotes es clave para la producción de islotes in vitro.
Objetivo del estudio:
- Para aclarar el proceso de desarrollo de los islotes pancreáticos y la morfogénesis.
- Investigar la relación entre la diferenciación endocrina y la estructura de los islotes.
- Explorar métodos para generar islotes funcionales in vitro.
Principales métodos:
- Se utilizó la secuenciación de ARNm de una sola célula para analizar el desarrollo de los islotes pancreáticos.
- Observación de la dinámica de migración y diferenciación de las células progenitoras.
- Inducción de estructuras semejantes a penínsulas en la diferenciación de células madre embrionarias humanas.
Principales resultados:
- Contrariamente al dogma, la morfología de los islotes y la diferenciación endocrina están directamente relacionadas.
- Los progenitores endocrinos diferenciados forman estructuras cohesionadas y parecidas a brotes llamadas "penínsulas".
- Las células alfa forman la capa externa, seguidas de las células beta, estableciendo una arquitectura de núcleo-manto.
Conclusiones:
- Existe una relación espacio-temporal directa entre la diferenciación endocrina y la morfogénesis de los islotes.
- La formación de penínsulas precede al desarrollo de la arquitectura de islotes maduros.
- La inducción exitosa de estructuras semejantes a penínsulas ofrece una vía para la generación de islotes enteros in vitro.
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