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TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors

2015; Nature Portfolio; Volume: 17; Issue: 5 Linguagem: Inglês

10.1038/ncb3160

1476-4679

Inês Cebola, Santiago A. Rodríguez‐Seguí, Candy H.-H. Cho, José Bessa, Meritxell Rovira, Mario Luengo, Mariya Chhatriwala, Andrew Berry, Joan Ponsa-Cobas, M.A. Maestro, Rachel Jennings, Lorenzo Pasquali, Ignasi Morán, N. Castro Unanua, Neil A. Hanley, José Luis Gómez-Skármeta, Ludovic Vallier, Jorge Ferrer,

Hippo pathway signaling and YAP/TAZ

The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas. By deciphering the transcriptional network of human embryonic pancreatic progenitors, Ferrer and colleagues identify the Hippo-responsive transcription factor TEAD1 as a regulator of the pancreatic progenitor enhancer programme.