PolNet Analysis: a software tool for the quantification of network-level endothelial cell polarity and blood flow during vascular remodelling

In this paper, we present PolNet, an open source software tool for the study of blood flow and cell-level biological activity during vessel morphogenesis. We provide an image acquisition, segmentation, and analysis protocol to quantify endothelial cell polarity in entire in vivo vascular networks. In combination, we use computational fluid dynamics to characterise the haemodynamics of the vascular networks under study. The tool enables, for the first time, network-level analysis of polarity and flow for individual endothelial cells. To date, PolNet has proven invaluable for the study of endothelial cell polarisation and migration during vascular patterning, as demonstrated by our recent papers [1, 2]. Additionally, the tool can be easily extended to correlate blood flow with other experimental observations at the cellular/molecular level. We release the source code of our tool under the LGPL licence.

[1]  Jeff W. Lichtman,et al.  Clarifying Tissue Clearing , 2015, Cell.

[2]  Raju Tomer,et al.  Light sheet microscopy in cell biology. , 2013, Methods in molecular biology.

[3]  M. Schwartz,et al.  Mechanotransduction in vascular physiology and atherogenesis , 2009, Nature Reviews Molecular Cell Biology.

[4]  H. H. Lipowsky,et al.  Microvascular Rheology and Hemodynamics , 2005, Microcirculation.

[5]  Gerhard Gompper,et al.  Modeling microcirculatory blood flow: current state and future perspectives , 2016, Wiley interdisciplinary reviews. Systems biology and medicine.

[6]  Axel R Pries,et al.  Modeling Structural Adaptation of Microcirculation , 2008, Microcirculation.

[7]  Holger Gerhardt,et al.  Dynamic Endothelial Cell Rearrangements Drive Developmental Vessel Regression , 2015, PLoS biology.

[8]  Aleksander S Popel,et al.  Microcirculation and Hemorheology. , 2005, Annual review of fluid mechanics.

[9]  Cornelia Denz,et al.  Endoglin controls blood vessel diameter through endothelial cell shape changes in response to haemodynamic cues , 2017, Nature Cell Biology.

[10]  S. Chien,et al.  Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. , 2011, Physiological reviews.

[11]  Holger Gerhardt,et al.  Basic and Therapeutic Aspects of Angiogenesis , 2011, Cell.

[12]  Martin Jones,et al.  Computer simulations reveal complex distribution of haemodynamic forces in a mouse retina model of angiogenesis , 2013, Journal of The Royal Society Interface.

[13]  K. Red-Horse,et al.  DACH1 stimulates shear stress-guided endothelial cell migration and coronary artery growth through the CXCL12–CXCR4 signaling axis , 2017, Genes & development.

[14]  E. Edelman,et al.  Prediction of the Localization of High-Risk Coronary Atherosclerotic Plaques on the Basis of Low Endothelial Shear Stress: An Intravascular Ultrasound and Histopathology Natural History Study , 2008, Circulation.

[15]  Rene,et al.  THE AMERICAN JOURNAL OF PHYSIOLOGY. , 1897, Science.

[16]  Finn Verner Jensen,et al.  Bayesian networks , 1998, Data Mining and Knowledge Discovery Handbook.

[17]  Chun Li,et al.  Haemodynamics-Driven Developmental Pruning of Brain Vasculature in Zebrafish , 2012, PLoS biology.

[18]  C. Betsholtz,et al.  Endoglin prevents vascular malformation by regulating flow-induced cell migration and specification through VEGFR2 signalling , 2017, Nature Cell Biology.