Kidney Week

Abstract: FR-OR047

Adult Mouse Aqp2+ Progenitor Cells Maintain and Remodel Connecting Tubule/Collecting Duct

Session Information

• Defining Cellular Composition and Mechanisms of Kidney Formation
  October 26, 2018 | Location: 4, San Diego Convention Center
  Abstract Time: 06:18 PM - 06:30 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 501 Development, Stem Cells, and Regenerative Medicine: Basic

Authors

• Gao, Chao, Albany Medical College, Albany, New York, United States

Chao Gao, PhD

• Zhang, Long, Albany Medical College, Albany, New York, United States

Long Zhang,

• Chen, Lihe, NIH, Bethesda, Maryland, United States

Lihe Chen,

• Chen, Enuo, Albany Medical College, Albany, New York, United States

Enuo Chen,

• Zhang, Wenzheng, Albany Medical College, Albany, New York, United States

Wenzheng Zhang,

Group or Team Name

• WZ Zhang lab

Background

Embryonic Aqp2⁺ progenitor cells generate all known cell types in the connecting tubule/collecting duct (CNT/CD). Aqp2^ECE/+ is a highly tamoxifen-inducible principal-cell-specific Cre mouse line with complete fidelity in cell specificity and no leakiness. Here we investigate weather Aqp2⁺ progenitor cells have multipotency and self-renewal potential during CNT/CD maintenance and lithium-induced remodeling in adult mice.

Methods

Adult Aqp2^ECE/+ RFP/+ and Aqp2ECE/+ rainbow/+ were induced with tamoxifen and examined at various time points post induction. Alternatively, tamoxifen-induced adult mice were treated with dietary LiCl for 4, 7 and 14 days, respectively. RFP or GFP co-expression with markers for PC (Aqp2), IC (V-ATPase B1, B2, CAII, AE1, and Pendrin) was investigated by immunofluorescence staining. PC to IC conversion rates (RFP⁺IC⁺/(RFP⁺IC⁺ + RFP⁺IC^-) and IC derivation from PC rates (RFP⁺IC⁺/(RFP⁺IC⁺ + RFP^-IC⁺) were determined. Uninterrupted single-colored clones in Aqp2ECE/+ rainbow/+ were grouped into single-cell and multiple-cell ones to represent regular and progenitor cell-like PC, respectively.

Results

Aqp2^ECE/+ RFP/+ possessed no PC to IC conversion (no RFP⁺ IC⁺ cells) at day 1, intermediate state cells (RFP+ PC+ IC+) at day 3, and completely converted cells (RFP+ PC- IC+) at day 60 and 270 post induction. The conversion rate was 5% in the cortex and 0.02% in the medulla at day 60, which were increased to 25% and 4%, respectively, at day 270. IC derivation from PC rates were 47% and 6% in the cortex and medulla, respectively, at day 270. Lithium progressively facilitated PC-IC conversion, with the highest conversion rate reaching to 17.3% in cortex at day 14. Among the total cortical IC population, about 31% IC were derived from PC. Clone size ranged from 1-7 cells, with the largest ones observed at day 270 post induction and day 14 post lithium treatment. The majority of clones were 1-2 cells.

Conclusion

Adult Aqp2⁺ progenitor cells possess multipotency and self-renewal potential, and contribute to CNT/CD maintenance and remodeling.

Funding

• NIDDK Support