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

Inês Cebola, Santiago A. Rodríguez-Seguí, Candy H.H. Cho, José Bessa, Meritxell Rovira, Mario Luengo, Mariya Chhatriwala, Andrew Berry, Joan Ponsa-Cobas, Miguel Angel Maestro, Rachel E. Jennings, Lorenzo Pasquali, Ignasi Morán, Natalia Castro, Neil A. Hanley, Jose Luis Gomez-Skarmeta, Ludovic Vallier, Jorge Ferrer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

149 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)615-626
Number of pages12
JournalNature Cell Biology
Issue number5
Publication statusPublished - 5 May 2015

Bibliographical note

Funding Information:
The research was supported by the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre. Work was funded by grants from the Ministerio de Economía y Competitividad (CB07/08/0021, SAF2011-27086, PLE2009-0162 to J.F., BFU2013-41322-P to J.L.G-S.), the Andalusian Government (BIO-396 to J.L.G-S.), the Wellcome Trust (WT088566 and WT097820 to N.A.H., WT101033 to J.F.), the Manchester Biomedical Research Centre, ERC advanced starting grant IMDs (C.H-H.C. and L.V.) and the Cambridge Hospitals National Institute for Health Research Biomedical Research Centre (L.V.). R.E.J. is a Medical Research Council clinical training fellow. The authors are grateful to C. Wright (Vanderbilt University) for zebrafish Pdx1 antiserum, J. Postlethwait (Purdue University) for a Sox9b clone, H. Sasaki (Kumamoto University) for a TEAD–EnR clone, C. Vinod and L. Abi for research nurse assistance, and clinical colleagues at Central Manchester University Hospitals NHS Foundation Trust. The authors thank J. Garcia-Hurtado for technical assistance (IDIBAPS).

Publisher Copyright:
© 2015 Macmillan Publishers Limited.

ASJC Scopus subject areas

  • Cell Biology


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