Does Multicolor Lineage Tracing of Endothelial Cells Provide a Black and White Answer on Clonal Expansion in Post-Natal Angiogenesis?
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Postnatal angiogenesis occurs in physiological (ie, blood vessel growth in muscle in response to exercise and with cyclic changes within menstrual tissue) and pathological conditions (eg, diabetic retinopathy). Many attempts to promote postnatal angiogenesis have been attempted to drive revascularization of ischemic tissues. Surprisingly, we continue to lack fundamental information on which endothelial cells possess replicative potential in blood vessels. Prior work established that infusion of H3 thymidine into young mammals revealed endothelial cell proliferation in small and large vessels that is high at birth, varies within and among organ vasculature, and declines rapidly over the first few weeks of life. In adult animals, the rate of homeostatic endothelial cell turnover has been quantified as <1% in rodents. Despite these pieces of information, we do not know specifics about the individual proliferative capacities of endothelial cells, whether this activity is restricted to a small subset or is a feature ubiquitously present within all endothelial cells in a blood vessel.1
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Manavski et al2 in this issue have used inducible endothelial cell–restricted multicolor reporter (Confetti) transgenic mice to interrogate the clonal expansion of individual endothelial cells within normally developing murine tissue vasculature or within tissues challenged by ischemia and hypoxia. This system has permitted quantification of all the endothelial cells within a fixed sampling volume of the tissue vasculature to detect an increase in local distribution of a singular color of endothelial cells within areas of clonal expansion compared with near equivalent levels of random color distribution in areas lacking clonal expansion. In brief, the authors failed to detect significant color enrichment (<10% clonal expansion) in the developing retinal vasculature at postnatal day 5, consistent with prior work in zebrafish that had identified random integration or cell mixing accounting for endothelial cell distributions in developmental …