Endothelial Progenitors Exist within the Kidney and Lung Mesenchyme.
Endothelial Progenitors Exist within the Kidney and Lung Mesenchyme.
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DOI：
10.1371/journal.pone.0065993
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Bates CM
中科院分区：
文献类型：
--
作者：
Sims-Lucas S;Schaefer C;Bushnell D;Ho J;Logar A;Prochownik E;Gittes G;Bates CM
肾内皮细胞一直被认为是由固有的成血管细胞前体细胞产生的，这些前体细胞从肾源性间充质（血管发生）和/或从侵入性血管（血管生成）转分化而来。虽然Foxd 1阳性肾皮质基质已显示分化为支持肾脏中血管系统的细胞（包括血管平滑肌和周细胞），但尚未将其视为内皮细胞祖细胞的来源。此外，目前还不清楚其他器官（如肺）中的Foxd 1阳性间充质细胞是否具有形成内皮的潜力。本研究探讨了肾脏和肺的Foxd 1阳性细胞产生内皮祖细胞的潜力。我们利用免疫荧光（IF）和荧光激活细胞分选（FACS）共同标记Foxd 1表达细胞（包括永久性谱系标记的细胞）与内皮标记物在胚胎和出生后的小鼠。我们还培养了FACsorted Foxd 1阳性细胞，进行体外内皮细胞小管形成试验，并检查了乙酰化低密度脂蛋白（Ac-LDL）的内吞作用，这是一种内皮细胞功能试验。免疫荧光和流式细胞仪显示，一个子集的Foxd 1阳性细胞从肾脏和肺共表达内皮细胞标记物在整个胚胎发生。在体外，培养的胚胎Foxd 1阳性细胞能够分化成表达内皮细胞标志物的管状网络，并能够内吞Ac-LDL。肾脏和肺中的IF和FACS显示，谱系标记的Foxd 1阳性细胞在出生后小鼠中产生了相当大一部分内皮细胞。在肾脏中，基质来源的细胞产生了一部分管周毛细血管内皮，但不是肾小球或大血管内皮。这些发现揭示了内皮细胞谱系的异质性;此外，发育中的肾脏和肺的Foxd 1阳性间充质细胞是内皮祖细胞的来源，这可能对血管系统的形成至关重要。
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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DOI：
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发表时间：
1996-05-01
影响因子：
4.2
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DOI：
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发表时间：
1998-07-01
影响因子：
4.2
作者：
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