A ROLE FOR ANGIOTENSIN CONVERTING ENZYME IN THE CHARACTERISATION, ENRICHMENT AND PROLIFERATION POTENTIAL OF ADULT MURINE PITUITARY COLONY FORMING CELLS

¹ Pituitary Research Unit, Murdoch Childrens Research Institute, Royal Childrens Hospital, Victoria, Australia
² Stem Cell Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
³ Flow Cytometry Unit, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
⁴ Max-Planck-Institut fur Experimentelle, Endokrinologie, Hannover, Germany
⁵ School of Molecular & Biomedical Science, The University of Adelaide, Adelaide, Australia

^* To whom correspondence should be addressed. E-mail: diana.lepore{at}mcri.edu.au.

	Abstract

Recently we described a rare cell type within the adult murine pituitary gland with progenitor cell hallmarks, (PCFCs). PCFCs are contained exclusively within a sub-population of cells that import fluorescent -Ala-Lys-N-7-amino-4-methylcoumarin-3-acetic acid (AMCA). 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 co-expressed on 38%. ACE(+)AMCA(+) cells enriched for PCFCs by 170-fold over unselected cells and colonies were 2-fold 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 unrecognised 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 sub-luminal zone, thus supporting previous proposals that the luminal zone is a source of precursor cells in the adult pituitary.

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