Embryogenesis of the First Circulating Endothelial Cells
Abstract
Prior to this study, the earliest appearance of circulating endothelial cells in warm-blooded animals was unknown. Time-lapse imaging of germ-line transformed Tie1-YFP reporter quail embryos combined with the endothelial marker antibody QH1 provides definitive evidence for the existence of circulating endothelial cells – from the very beginning of blood flow. Blood-smear counts of circulating cells from Tie1-YFP embryos showed that up to 30% of blood-borne cells are Tie1 positive; though cells expressing low levels of YFP were also positive for benzidine, a hemoglobin stain, suggesting that these cells were differentiating into erythroblasts. Electroporation-based time-lapse experiments, exclusively targeting the intra-embryonic mesoderm were combined with QH1 immunostaining. The latter antibody marks quail endothelial cells. Together the optical data provide conclusive evidence that endothelial cells can enter blood flow from vessels of the embryo proper, as well as from extra-embryonic areas. When Tie1-YFP positive cells and tissues are transplanted to wild type host embryos, fluorescent cells emigrate from such transplants and join host vessels; subsequently a few YFP cells are shed into circulation. These data establish that entering circulation is a commonplace activity of embryonic vascular endothelial cells. We conclude that in the class of vertebrates most closely related to mammals a normal component of primary vasculogenesis is production of endothelial cells that enter circulation from all vessels, both intra- and extra-embryonic.
Additional Information
© 2013 Cui et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: May 14, 2012; Accepted: March 5, 2013; Published: May 30, 2013. This work was supported by the National Institutes of Health R01 grants HL085694 (BJR), HL068855 (CDL) (http://www.nih.gov/); the G. Harold & Leila Y. Mathers Charitable Foundation (BJR and CDL) (http://www.mathersfoundation.org/); a NSERC Discovery 342134 (EAVJ) (http://www.nserc-crsng.gc.ca); and an American Heart Assoc, postdoctoral fellowship (0620105Z) to CC (http://www.heart.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author Contributions: Conceived and designed the experiments: CC MBF EAVJ BJR CDL. Performed the experiments: CC MBF RL TC SA. Analyzed the data: CC MBF EAVJ RL TC SA BJR CDL. Contributed reagents/materials/ analysis tools: CC EAVJ RL BJR CDL. Wrote the paper: CC MBF EAVJ RL AR BJR CDL.Attached Files
Published - journal.pone.0060841.pdf
Supplemental Material - journal.pone.0060841.s001.tif
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Additional details
- PMCID
- PMC3667859
- Eprint ID
- 40749
- Resolver ID
- CaltechAUTHORS:20130821-090748059
- HL085694
- NIH
- HL068855
- NIH
- G. Harold & Leila Y. Mathers Charitable Foundation
- 342134
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- 0620105Z
- American Heart Association
- Created
-
2013-08-21Created from EPrint's datestamp field
- Updated
-
2021-11-10Created from EPrint's last_modified field