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

doi:10.1038/ncb3160

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 journal › Article › peer-review

149 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	615-626
Number of pages	12
Journal	Nature Cell Biology
Volume	17
Issue number	5
DOIs	https://doi.org/10.1038/ncb3160
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cebola, I., Rodríguez-Seguí, S. A., Cho, C. H. H., Bessa, J., Rovira, M., Luengo, M., Chhatriwala, M., Berry, A., Ponsa-Cobas, J., Maestro, M. A., Jennings, R. E., Pasquali, L., Morán, I., Castro, N., Hanley, N. A., Gomez-Skarmeta, J. L., Vallier, L., & Ferrer, J. (2015). TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors. Nature Cell Biology, 17(5), 615-626. https://doi.org/10.1038/ncb3160

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title = "TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors",

abstract = "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.",

author = "In{\^e}s Cebola and Rodr{\'i}guez-Segu{\'i}, {Santiago A.} and Cho, {Candy H.H.} and Jos{\'e} Bessa and Meritxell Rovira and Mario Luengo and Mariya Chhatriwala and Andrew Berry and Joan Ponsa-Cobas and Maestro, {Miguel Angel} and Jennings, {Rachel E.} and Lorenzo Pasquali and Ignasi Mor{\'a}n and Natalia Castro and Hanley, {Neil A.} and Gomez-Skarmeta, {Jose Luis} and Ludovic Vallier and Jorge Ferrer",

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 Econom{\'i}a 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: {\textcopyright} 2015 Macmillan Publishers Limited.",

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Cebola, I, Rodríguez-Seguí, SA, Cho, CHH, Bessa, J, Rovira, M, Luengo, M, Chhatriwala, M, Berry, A, Ponsa-Cobas, J, Maestro, MA, Jennings, RE, Pasquali, L, Morán, I, Castro, N, Hanley, NA, Gomez-Skarmeta, JL, Vallier, L & Ferrer, J 2015, 'TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors', Nature Cell Biology, vol. 17, no. 5, pp. 615-626. https://doi.org/10.1038/ncb3160

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T1 - TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors

AU - Cebola, Inês

AU - Rodríguez-Seguí, Santiago A.

AU - Cho, Candy H.H.

AU - Bessa, José

AU - Rovira, Meritxell

AU - Luengo, Mario

AU - Chhatriwala, Mariya

AU - Berry, Andrew

AU - Ponsa-Cobas, Joan

AU - Maestro, Miguel Angel

AU - Jennings, Rachel E.

AU - Pasquali, Lorenzo

AU - Morán, Ignasi

AU - Castro, Natalia

AU - Hanley, Neil A.

AU - Gomez-Skarmeta, Jose Luis

AU - Vallier, Ludovic

AU - Ferrer, Jorge

N1 - 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.

PY - 2015/5/5

Y1 - 2015/5/5

N2 - 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.

AB - 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.

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DO - 10.1038/ncb3160

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AN - SCOPUS:84928938629

SN - 1465-7392

VL - 17

SP - 615

EP - 626

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 5

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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