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Endothelial Progenitors Exist within the Kidney and Lung Mesenchyme

Sims-Lucas, S and Schaefer, C and Bushnell, D and Ho, J and Logar, A and Prochownik, E and Gittes, G and Bates, CM (2013) Endothelial Progenitors Exist within the Kidney and Lung Mesenchyme. PLoS ONE, 8 (6).

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Abstract

The renal endothelium has been debated as arising from resident hemangioblast precursors that transdifferentiate from the nephrogenic mesenchyme (vasculogenesis) and/or from invading vessels (angiogenesis). While the Foxd1-positive renal cortical stroma has been shown to differentiate into cells that support the vasculature in the kidney (including vascular smooth muscle and pericytes) it has not been considered as a source of endothelial cell progenitors. In addition, it is unclear if Foxd1-positive mesenchymal cells in other organs such as the lung have the potential to form endothelium. This study examines the potential for Foxd1-positive cells of the kidney and lung to give rise to endothelial progenitors. We utilized immunofluorescence (IF) and fluorescence-activated cell sorting (FACS) to co-label Foxd1-expressing cells (including permanently lineage-tagged cells) with endothelial markers in embryonic and postnatal mice. We also cultured FACsorted Foxd1-positive cells, performed in vitro endothelial cell tubulogenesis assays and examined for endocytosis of acetylated low-density lipoprotein (Ac-LDL), a functional assay for endothelial cells. Immunofluorescence and FACS revealed that a subset of Foxd1-positive cells from kidney and lung co-expressed endothelial cell markers throughout embryogenesis. In vitro, cultured embryonic Foxd1-positive cells were able to differentiate into tubular networks that expressed endothelial cell markers and were able to endocytose Ac-LDL. IF and FACS in both the kidney and lung revealed that lineage-tagged Foxd1-positive cells gave rise to a significant portion of the endothelium in postnatal mice. In the kidney, the stromal-derived cells gave rise to a portion of the peritubular capillary endothelium, but not of the glomerular or large vessel endothelium. These findings reveal the heterogeneity of endothelial cell lineages; moreover, Foxd1-positive mesenchymal cells of the developing kidney and lung are a source of endothelial progenitors that are likely critical to patterning the vasculature. © 2013 Sims-Lucas et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Sims-Lucas, S
Schaefer, Ccms198@pitt.eduCMS198
Bushnell, Ddab152@pitt.eduDAB152
Ho, Jjah186@pitt.eduJAH186
Logar, A
Prochownik, Eevp4@pitt.eduEVP4
Gittes, Ggkg2@pitt.eduGKG2
Bates, CMcmb127@pitt.eduCMB127
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorSingh, Shree RamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 18 June 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 6
DOI or Unique Handle: 10.1371/journal.pone.0065993
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
School of Medicine > Pediatrics
Refereed: Yes
Date Deposited: 15 Jul 2013 20:24
Last Modified: 02 Feb 2019 16:56
URI: http://d-scholarship.pitt.edu/id/eprint/19199

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