Abstract: FR-PO938
Abcg2-Expressing Endothelial Cells Contribute to Kidney Postnatal Vascular Growth and Maintenance
Session Information
- Development, Stem Cells, Regenerative Medicine - II
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 501 Development, Stem Cells, and Regenerative Medicine: Basic
Authors
- Go, Ellen, Indiana University, Indianapolis, Indiana, United States
- Lin, Yang, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Yoder, Mervin C., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Basile, David P., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background
Tissue blood vessels are lined by endothelial cells (EC) with heterogeneous states of proliferative potential. Several groups have recently identified resident vascular endothelial stem cells (VESC) and confirmed their critical role in vascular growth as they are highly proliferative, give rise to clonal endothelial colonies and are able to form vessels upon in vivo transplantation into sites of ischemia and hypoxia. Many other tissue resident stem cells express the ATP-binding cassette family drug transporter, Abcg2. We examined if Abcg2-expressing EC contribute to development of the kidney vasculature.
Methods
We crossed Abcg2CreERT2 knock-in mice, which faithfully express Cre in Abcg2-expressing cells, with ROSATdTomato transgenic reporter mice to make Abcg2TT mice. TdTomato labels Abcg2-expressing cells and their progenies upon tamoxifen injection. We performed lineage tracing studies by injecting Abcg2TT mice at postnatal day 0 (neonate) or 42 (adult). Flow cytometry analysis of TdTomato+ EC was performed at days 1, 7, 21 and 56 post-tamoxifen in neonates, and days 1, 42 and 84 post-tamoxifen in adults. MACS-sorted EC from transgenic mice one day after tamoxifen injection were plated on OP-9 cultures and examined for the presence of endothelial colonies after 14 days.
Results
In neonates, 8.3±1.7% of total EC expressed TdTomato one day after tamoxifen injection. After 7 days, this population contributed to 36.0±11.1% of all kidney EC. In adult mice, 2.9±1.3% of total EC was labeled one day after a single tamoxifen injection. This population contributed to 15.4±2.9% of total kidney EC after 84 days. BrdU labeling studies are currently examining whether the turnover of kidney EC during these stages of development are derived from this population. The frequency of colony formation of TdTomato labeled EC is significantly higher than non-labeled EC.
Conclusion
Neonate and adult murine kidney blood vessels contain Abcg2-expressing EC that contribute to kidney vessel growth during development and maintenance of kidney vessel homeostasis in vivo. Thus, Abcg2-expressing EC may represent kidney VESC.
Funding
- Private Foundation Support