Format

Send to

Choose Destination
Nat Commun. 2017 Sep 28;8(1):726. doi: 10.1038/s41467-017-00738-7.

Transcriptional regulation of endothelial cell behavior during sprouting angiogenesis.

Author information

1
Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149, Münster, Germany.
2
Faculty of Medicine, University of Münster, 48149, Münster, Germany.
3
Laboratory of Regulatory Genomics, Max-Planck-Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149, Münster, Germany.
4
Department of Cell and Developmental Biology, Max-Planck-Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149, Münster, Germany.
5
Laboratory of Regulatory Genomics, Max-Planck-Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149, Münster, Germany. jmv@mpi-muenster.mpg.de.
6
Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149, Münster, Germany. ralf.adams@mpi-muenster.mpg.de.
7
Faculty of Medicine, University of Münster, 48149, Münster, Germany. ralf.adams@mpi-muenster.mpg.de.

Abstract

Mediating the expansion of vascular beds in many physiological and pathological settings, angiogenesis requires dynamic changes in endothelial cell behavior. However, the molecular mechanisms governing endothelial cell activity during different phases of vascular growth, remodeling, maturation, and quiescence remain elusive. Here, we characterize dynamic gene expression changes during postnatal development and identify critical angiogenic factors in mouse retinal endothelial cells. Using actively translating transcriptome analysis and in silico computational analyses, we determine candidate regulators controlling endothelial cell behavior at different developmental stages. We further show that one of the identified candidates, the transcription factor MafB, controls endothelial sprouting in vitro and in vivo, and perform an integrative analysis of RNA-Seq and ChIP-Seq data to define putative direct MafB targets, which are activated or repressed by the transcriptional regulator. Together, our results identify novel cell-autonomous regulatory mechanisms controlling sprouting angiogenesis.Angiogenesis is a complex process that requires coordinated changes in endothelial cell behavior. Here the authors use Ribo-tag and RNA-Seq to determine temporal profiles of transcriptional activity during postnatal retinal angiogenesis, identifying transcriptional regulators of the process.

PMID:
28959057
PMCID:
PMC5620061
DOI:
10.1038/s41467-017-00738-7
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center