Endothelial Progenitors Exist within the Kidney and Lung Mesenchyme.

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 tha...

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Main Authors: Sunder Sims-Lucas, Caitlin Schaefer, Daniel Bushnell, Jacqueline Ho, Alison Logar, Edward Prochownik, George Gittes, Carlton M Bates
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3688860?pdf=render
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author Sunder Sims-Lucas
Caitlin Schaefer
Daniel Bushnell
Jacqueline Ho
Alison Logar
Edward Prochownik
George Gittes
Carlton M Bates
author_facet Sunder Sims-Lucas
Caitlin Schaefer
Daniel Bushnell
Jacqueline Ho
Alison Logar
Edward Prochownik
George Gittes
Carlton M Bates
author_sort Sunder Sims-Lucas
collection DOAJ
description 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.
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spelling doaj.art-af53d293bc5d4def9c407868aea1ca7e2022-12-21T18:32:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6599310.1371/journal.pone.0065993Endothelial Progenitors Exist within the Kidney and Lung Mesenchyme.Sunder Sims-LucasCaitlin SchaeferDaniel BushnellJacqueline HoAlison LogarEdward ProchownikGeorge GittesCarlton M BatesThe 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.http://europepmc.org/articles/PMC3688860?pdf=render
spellingShingle Sunder Sims-Lucas
Caitlin Schaefer
Daniel Bushnell
Jacqueline Ho
Alison Logar
Edward Prochownik
George Gittes
Carlton M Bates
Endothelial Progenitors Exist within the Kidney and Lung Mesenchyme.
PLoS ONE
title Endothelial Progenitors Exist within the Kidney and Lung Mesenchyme.
title_full Endothelial Progenitors Exist within the Kidney and Lung Mesenchyme.
title_fullStr Endothelial Progenitors Exist within the Kidney and Lung Mesenchyme.
title_full_unstemmed Endothelial Progenitors Exist within the Kidney and Lung Mesenchyme.
title_short Endothelial Progenitors Exist within the Kidney and Lung Mesenchyme.
title_sort endothelial progenitors exist within the kidney and lung mesenchyme
url http://europepmc.org/articles/PMC3688860?pdf=render
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