YAP-TEAD regulates the super-enhancer network to control early surface ectoderm commitment.

Area of Science:

• Genomics
• Stem Cell Biology
• Developmental Biology

Background:

• Super enhancers (SEs) are critical for cellular identity and function.
• Understanding SEs in surface ectoderm differentiation is vital for regenerative medicine.

Purpose of the Study:

• To profile the SE landscape in surface ectoderm cells derived from pluripotent stem cells.
• To investigate the regulatory network controlling SEs and their role in differentiation.
• To identify key regulators of surface ectoderm commitment.

Main Methods:

• Profiling SE landscape using 3D genomics.
• CRISPR-dCas9 for SE perturbation.
• Analysis of transcription factor regulatory networks.
• Investigating YAP-TEAD signaling pathway.

Main Results:

• Identified active histone modifications and chromatin interactions of SEs.
• Perturbing SEs decreased target gene expression.
• Uncovered a regulatory network involving core TFs and TEAD1.
• YAP-TEAD activation expedited differentiation and SE establishment.

Conclusions:

• SEs play a crucial role in surface ectoderm lineage commitment.
• YAP-TEAD signaling is a vital regulator of this process.
• Findings provide insights into lineage commitment and stem cell-based epithelial regeneration.