A role for angiotensin-converting enzyme in the characterization, enrichment, and proliferation potential of adult murine pituitary colony-forming cells

Recently, we described a rare cell type within the adult murine pituitary gland with progenitor cell hallmarks (PCFCs). PCFCs are contained exclusively within a subpopulation of cells that import fluorescent β-Ala-Lys-Nε- AMCA (7-amino-4-methylcoumarin-3-acetic acid). Herein, we investigate the utility of cell surface molecules angiotensin-converting enzyme (ACE) and stem cell antigen-1 (Sca-1) to further enrich for PCFCs. ACE and Sca-1 were expressed on 61% and 55% of AMCA⁺CD45^-CD31^- cells, respectively, and coexpressed on 38%. ACE⁺Sca-1⁺AMCA ⁺ cells enriched for PCFCs by 195-fold over unselected cells. ACE⁺AMCA⁺ cells enriched for PCFCs by 170-fold, and colonies were twofold larger than for AMCA⁺ selection alone. Conversely, ACE^--selected cells reduced both colony-forming activity and size. Notably, colonies generated from AMCA⁺ cells obtained from ACE^null mice were 2.7-fold smaller than for wild-type mice. These data identify ACE as a previously unrecognized marker of PCFCs and suggest that ACE is functionally important for PCFC proliferation. Anatomically, the cells that imported AMCA and expressed ACE were situated in the marginal epithelial cell layer of the pituitary cleft and in the adjacent subluminal zone, thus supporting previous proposals that the luminal zone is a source of precursor cells in the adult pituitary.