Publication

Dynamic chromatin organization and regulatory interactions in human endothelial cell differentiation.

current
   December 12th, 2022 at 10:17pm

Overview


Abstract

Vascular endothelial cells are a mesoderm-derived lineage with many essential functions, including angiogenesis and coagulation. The gene-regulatory mechanisms underpinning endothelial specialization are largely unknown, as are the roles of chromatin organization in regulating endothelial cell transcription. To investigate the relationships between chromatin organization and gene expression, we induced endothelial cell differentiation from human pluripotent stem cells and performed Hi-C and RNA-sequencing assays at specific time points. Long-range intrachromosomal contacts increase over the course of differentiation, accompanied by widespread heteroeuchromatic compartment transitions that are tightly associated with transcription. Dynamic topologically associating domain boundaries strengthen and converge on an endothelial cell state, and function to regulate gene expression. Chromatin pairwise point interactions (DNA loops) increase in frequency during differentiation and are linked to the expression of genes essential to vascular biology. Chromatin dynamics guide transcription in endothelial cell development and promote the divergence of endothelial cells from cardiomyocytes.

Authors

Alavattam KG  •  Mitzelfelt KA  •  Bonora G  •  Fields PA  •  Yang X  •  Chiu HS  •  Pabon L  •  Bertero A  •  Palpant NJ  •  Noble WS  •  Murry CE

Link

https://www.ncbi.nlm.nih.gov/pubmed/36493778


Journal

Stem cell reports

PMID:36493778

Published

December 2nd, 2022