Sca-1 identifies a trophoblast population with multipotent potential in the mid-gestation mouse placenta

Trophoblast stem (TS) cells in the mouse derive from the polar trophectoderm of the blastocyst and persist through early gestation (to E8.5) to support placental development. Further development and growth is proposed to rely on layer-restricted progenitor cells. Stem cell antigen (Sca) -1 is a member of the Ly6 gene family and a known marker of stem cells in both hematopoietic and non-hematopoietic mouse tissues. Having identified that Sca-1 mRNA was highly expressed in mouse TS cells in culture, we found that it was also expressed in a subset of trophoblast within the chorion and labyrinth layer of the mouse placenta. Isolation and in vitro culture of Sca-1(+) trophoblast cells from both differentiated TS cell cultures and dissected mouse placentae resulted in proliferating colonies that expressed known markers of TS cells. Furthermore, these cells could be stimulated to differentiate and expressed markers of both junctional zone and labyrinth trophoblast subtypes in a manner comparable to established mouse TS cell lines. Our results suggest that we have identified a subpopulation of TS cell-like cells that persist in the mid- to late- gestation mouse placenta as well as a cell surface protein that can be used to identify and isolate these cells.