TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors
Author(s)
Type
Journal Article
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.
Date Issued
2015-04-27
Date Acceptance
2015-03-13
Citation
Nature Cell Biology, 2015, 17 (5), pp.615-626
ISSN
1476-4679
Publisher
Nature Publishing Group
Start Page
615
End Page
626
Journal / Book Title
Nature Cell Biology
Volume
17
Issue
5
Copyright Statement
© 2015 Macmillan Publishers Limited. All rights reserved.
Sponsor
Wellcome Trust
Imperial College Healthcare NHS Trust- BRC Funding
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Medical Research Council (MRC)
Identifier
https://www.nature.com/articles/ncb3160
Grant Number
101033/C/13/Z
RDC03 79560
MR/L02036X/1
RDB03 79560
RDC03 79560
MR/L02036X/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
BETA-CELL DIFFERENTIATION
STEM-CELLS
TRANSCRIPTOME ANALYSIS
DUCTAL ADENOCARCINOMA
IN-VIVO
ZEBRAFISH
ORGANOGENESIS
EXPRESSION
AGENESIS
SOX9
Adaptor Proteins, Signal Transducing
Animals
Animals, Genetically Modified
Cell Differentiation
Cell Lineage
Cell Proliferation
Cells, Cultured
Computational Biology
DNA-Binding Proteins
Databases, Genetic
Embryonic Stem Cells
Gene Expression Regulation, Developmental
Gene Regulatory Networks
Humans
Mice, Inbred C57BL
Multipotent Stem Cells
Nuclear Proteins
Organogenesis
Pancreas
Phenotype
Phosphoproteins
RNA, Messenger
Signal Transduction
Time Factors
Transcription Factors
Zebrafish
Pancreas
Cells, Cultured
Multipotent Stem Cells
Animals
Mice, Inbred C57BL
Animals, Genetically Modified
Zebrafish
Humans
Adaptor Proteins, Signal Transducing
DNA-Binding Proteins
Nuclear Proteins
Phosphoproteins
Transcription Factors
RNA, Messenger
Computational Biology
Signal Transduction
Cell Differentiation
Cell Proliferation
Gene Expression Regulation, Developmental
Cell Lineage
Organogenesis
Phenotype
Time Factors
Databases, Genetic
Embryonic Stem Cells
Gene Regulatory Networks
Developmental Biology
06 Biological Sciences
11 Medical and Health Sciences
Date Publish Online
2015-04-27