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

Publisher: Macmillan Magazines Ltd Country of Publication: England NLM ID: 100890575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4679 (Electronic) Linking ISSN: 14657392 NLM ISO Abbreviation: Nat Cell Biol Subsets: MEDLINE

Original Publication: London : Macmillan Magazines Ltd., [1999-

Signal Transduction*; Adaptor Proteins, Signal Transducing/*metabolism ; DNA-Binding Proteins/*metabolism ; Embryonic Stem Cells/*metabolism ; Multipotent Stem Cells/*metabolism ; Nuclear Proteins/*metabolism ; Pancreas/*metabolism ; Phosphoproteins/*metabolism ; Transcription Factors/*metabolism; Adaptor Proteins, Signal Transducing/genetics ; Animals ; Animals, Genetically Modified ; Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Cells, Cultured ; Computational Biology ; DNA-Binding Proteins/genetics ; Databases, Genetic ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Humans ; Mice, Inbred C57BL ; Nuclear Proteins/genetics ; Organogenesis ; Pancreas/embryology ; Phenotype ; Phosphoproteins/genetics ; RNA, Messenger/metabolism ; TEA Domain Transcription Factors ; Time Factors ; Transcription Factors/genetics ; YAP-Signaling Proteins ; Zebrafish/embryology ; Zebrafish/genetics ; Zebrafish/metabolism

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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WT097820 United Kingdom WT_ Wellcome Trust; United Kingdom DH_ Department of Health; G0701448 United Kingdom MRC_ Medical Research Council; 101033 United Kingdom WT_ Wellcome Trust; G1100420 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust; G1000847 United Kingdom MRC_ Medical Research Council; 97922 United Kingdom WT_ Wellcome Trust; G0800784 United Kingdom MRC_ Medical Research Council; MR/L02036X/1 United Kingdom MRC_ Medical Research Council; 088566 United Kingdom WT_ Wellcome Trust

Indexing Agency: NLM Local ID #: EMS62644.

0 (Adaptor Proteins, Signal Transducing)
0 (DNA-Binding Proteins)
0 (Nuclear Proteins)
0 (Phosphoproteins)
0 (RNA, Messenger)
0 (TEA Domain Transcription Factors)
0 (TEAD1 protein, human)
0 (Transcription Factors)
0 (YAP-Signaling Proteins)
0 (YAP1 protein, human)

Date Created: 20150428 Date Completed: 20150709 Latest Revision: 20240610

20240610

PMC4434585

10.1038/ncb3160

25915126