Journal
SCIENCE ADVANCES
Volume 8, Issue 28, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abo5668
Keywords
-
Categories
Funding
- Projects of International Cooperation and Exchanges National Natural Science Foundation of China (NSFC) [32061160364]
- NSFC [81721003]
- Guangdong Innovative and Entrepreneurial Research Team Program [2016ZT06S029]
Ask authors/readers for more resources
This study investigates the regulatory network involved in the acquisition of cell fate, focusing on the induction of surface epithelium from human embryonic stem cells. By analyzing changes in morphology-related genes and the remodeling of the cytoskeleton, the study identifies grainyhead-like 3 (GRHL3) as an initiation factor that drives the commitment to surface epithelium fate. Furthermore, the study uncovers a positive feedback loop between GRHL3 and bone morphogenetic protein 4 in regulating surface epithelium fate decisions.
Understanding the regulatory network of cell fate acquisition remains a major challenge. Using the induction of surface epithelium (SE) from human embryonic stem cells as a paradigm, we show that the dynamic changes in morphologyrelated genes (MRGs) closely correspond to SE fate transitions. The marked remodeling of cytoskeleton indicates the initiation of SE differentiation. By integrating promoter interactions, epigenomic features, and transcriptome, we delineate an SE-specific cis-regulatory network and identify grainyhead-like 3 (GRHL3) as an initiation factor sufficient to drive SE commitment. Mechanically, GRHL3 primes the SE chromatin accessibility landscape and activates SE-initiating gene expression. In addition, the evaluation of GRHL3-mediated promoter interactions unveils a positive feedback loop of GRHL3 and bone morphogenetic protein 4 on SE fate decisions. Our work proposes a concept that MRGs could be used to identify cell fate transitions and provides insights into regulatory principles of SE lineage development and stem cell-based regenerative medicine.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available