The endometrium is the highly
regenerative lining of the uterus and contains small populations of epithelial
and stromal cells with stem/progenitor properties. However the lack of a
traceable marker for endometrial stem/progenitor cells in mouse models has
meant their role in endometrial regeneration is unclear. Telomerase activity
preserves stem/progenitor cell viability by maintaining telomere length during
repeated cycles of cell division. We have used the expression of mouse
telomerase reverse transcriptase (mTert), the rate limiting catalytic component
of the telomerase complex, as a marker to identify progenitor cells in the mouse
endometrium. GFP expression driven by the mTert promoter marks an infrequent
population of intrinsic (CD45negative) endometrial stromal cells
during development and adulthood, and rare focal regions of epithelium in the adult
endometrium. These mTert expressing cells are distinct from the stromal and
epithelial label-retaining cells previously described in the mouse endometrium.
mTert endometrial cells do not express estrogen
receptor-alpha or undergo proliferation in response to estrogen. However a
close spatial relationship between mTert positive epithelial cells and
proliferating epithelial cells suggests that mTert cells may give rise to
proliferative epithelial transit amplifying cells. We used inducible Cre recombinase
expression driven by the mTert promoter to permanently label the endometrial mTert
lineage with LacZ expression in postnatal mice. The mTert lineage is confined
to the stroma of prepubertal endometrium, but contributes to glandular and
luminal epithlelium in adult endometrium cycling under the influence of ovarian
hormones. Depriving the adult endometrium of hormones through ovariectomy causes
endometrial atrophy and prevents the epithelial expansion of the mTert lineage.
These results suggest that epithelial structures of the adult cycling endometrium
originate from an mTert positive stromal progenitor that undergoes
mesenchymal-to-epithelial transition during endometrial regeneration. This is
the first report of a traceable marker for endometrial progenitors with
epithelial differentiation potential.