A role of stochastic phenotype switching in generating mosaic endothelial cell heterogeneity

Lei Yuan, Gary C. Chan, David Beeler, Lauren Janes, Katherine C. Spokes, Harita Dharaneeswaran, Anahita Mojiri, William J. Adams, Tracey Sciuto, Guillermo Garcia-Cardeña, Grietje Molema, Peter M. Kang, Nadia Jahroudi, Philip A. Marsden, Ann Dvorak, Erzsébet Ravasz Regan () and William C. Aird ()
Additional contact information
Lei Yuan: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center
Gary C. Chan: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center
David Beeler: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center
Lauren Janes: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center
Katherine C. Spokes: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center
Harita Dharaneeswaran: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center
Anahita Mojiri: University of Alberta
William J. Adams: Beth Israel Deaconess Medical Center
Tracey Sciuto: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center
Guillermo Garcia-Cardeña: Center for Excellence in Vascular Biology, Brigham and Women's Hospital
Grietje Molema: Medical Biology Section, University Medical Center Groningen, University of Groningen
Peter M. Kang: Beth Israel Deaconess Medical Center
Nadia Jahroudi: University of Alberta
Philip A. Marsden: University of Toronto
Ann Dvorak: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center
Erzsébet Ravasz Regan: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center
William C. Aird: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center

Nature Communications, 2016, vol. 7, issue 1, 1-16

Abstract: Abstract Previous studies have shown that biological noise may drive dynamic phenotypic mosaicism in isogenic unicellular organisms. However, there is no evidence for a similar mechanism operating in metazoans. Here we show that the endothelial-restricted gene, von Willebrand factor (VWF), is expressed in a mosaic pattern in the capillaries of many vascular beds and in the aorta. In capillaries, the mosaicism is dynamically regulated, with VWF switching between ON and OFF states during the lifetime of the animal. Clonal analysis of cultured endothelial cells reveals that dynamic mosaic heterogeneity is controlled by a low-barrier, noise-sensitive bistable switch that involves random transitions in the DNA methylation status of the VWF promoter. Finally, the hearts of VWF-null mice demonstrate an abnormal endothelial phenotype as well as cardiac dysfunction. Together, these findings suggest a novel stochastic phenotype switching strategy for adaptive homoeostasis in the adult vasculature.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms10160 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10160

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10160

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().