Dynamic chromatin organization and regulatory interactions in human endothelial cell differentiation
Stem Cell Reports. 2023-01-10;18(1):159-174.
- 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.
Related data
- Available data
- website
- Data summary
- Data have been deposited in the 4DN data portal and are publicly available at https://data.4dnucleome.org/Alavattam-Mitzelfelt-endothelial-differentiation-chromatin
- Available data
- website
- Data summary
- Previously published CM differentiation data are available from GEO: GSE106690 (Bertero et al., 2019)
- Available data
- website
- Data summary
- Source code for analyses performed in this study is available at github.com/Noble-Lab/2020_kga0_endothelial-diff