Aquaporin 2-labeled cells differentiate to intercalated cells in response to potassium depletion

Histochem Cell Biol. 2016 Jan;145(1):17-24. doi: 10.1007/s00418-015-1372-9. Epub 2015 Oct 26.


The mammalian renal collecting duct consists of principal cells (PCs) and intercalated cells (ICs). Both PCs and ICs are involved in potassium (K(+)) homeostasis, PCs through their role in K(+) secretion and ICs through their ability to facilitate K(+) resorption. We previously hypothesized that PCs may differentiate into ICs upon K(+) depletion. However, no direct evidence has yet been obtained to conclusively demonstrate that PCs differentiate into ICs in response to K(+) depletion. Here, we present direct evidence for the differentiation of PCs into ICs by cell lineage tracing using aquaporin 2 (AQP2)-Cre mice and R26R-EYFP transgenic mice. In control mice, AQP2-EYFP(+) cells exhibited mainly a PC phenotype (AQP2-positive/H(+)-ATPase-negative). Interestingly, some AQP2-EYFP(+) cells exhibited an IC phenotype (H(+)-ATPase-positive/AQP2-negative); these cells accounted for 1.7 %. After K(+) depletion, the proportion of AQP2-EYFP(+) cells with an IC phenotype was increased to 4.1 %. Furthermore, some AQP2-EYFP(+) cells exhibited a "null cell" phenotype (AQP2-negative/H(+)-ATPase-negative) after K(+) depletion. Collectively, our data demonstrate that AQP2-labeled cells can differentiate into ICs, as well as null cells, in response to K(+) depletion. This finding indicates that some of AQP2-labeled cells possess properties of progenitor cells and that they can differentiate into ICs in the adult mouse kidney.

Keywords: Aquaporin; Differentiation; Intercalated cells; Principal cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 2 / genetics*
  • Bacterial Proteins / genetics
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Epithelial Cells / cytology*
  • Kidney Tubules, Collecting / cytology*
  • Luminescent Proteins / genetics
  • Mice
  • Mice, Knockout
  • Potassium / metabolism*


  • Aqp2 protein, mouse
  • Aquaporin 2
  • Bacterial Proteins
  • Luminescent Proteins
  • yellow fluorescent protein, Bacteria
  • Potassium