Related Experiment Video
Updated: May 15, 2026

Genome Editing and Directed Differentiation of hPSCs for Interrogating Lineage Determinants in Human Pancreatic Development
Published on: March 5, 2017
Dynamic chromatin remodeling mediated by polycomb proteins orchestrates pancreatic differentiation of human embryonic
Ruiyu Xie1, Logan J Everett, Hee-Woong Lim
1Department of Pediatrics and Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA 92093-0695, USA.
Abstract:
Embryonic development is characterized by dynamic changes in gene expression, yet the role of chromatin remodeling in these cellular transitions remains elusive. To address this question, we profiled the transcriptome and select chromatin modifications at defined stages during pancreatic endocrine differentiation of human embryonic stem cells. We identify removal of Polycomb group (PcG)-mediated repression on stage-specific genes as a key mechanism for the induction of developmental regulators. Furthermore, we discover that silencing of transitory genes during lineage progression associates with reinstatement of PcG-dependent repression. Significantly, in vivo- but not in vitro-differentiated endocrine cells exhibit close similarity to primary human islets in regard to transcriptome and chromatin structure. We further demonstrate that endocrine cells produced in vitro do not fully eliminate PcG-mediated repression on endocrine-specific genes, probably contributing to their malfunction. These studies reveal dynamic chromatin remodeling during developmental lineage progression and identify possible strategies for improving cell differentiation in culture.
Related Concept Videos
Chromatin Modification in iPS Cells
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Forced Transdifferentiation
Artificial transdifferentiation occurs...
Methods of Nuclear Reprogramming
Maintenance of the ES Cell State
Somatic to iPS Cell Reprogramming
Combinatorial Gene Control
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...

