Extracellular matrix influences gene expression and differentiation of mouse trophoblast stem cells.

Trophoblast stem (TS) cells were first isolated from the mouse placenta; however, little is known about their maintenance and niche in vivo. TS cells, like other stem cells, have a unique microenvironment in which the extracellular matrix (ECM) is a component. Placental pathology is associated with ECM change. However, how these changes and the individual ECM components impact the maintenance or differentiation of TS cells, has not been established. This study identified which ECM component(s) maintain undifferentiated mTS cells and which alter their differentiation profile. Additionally, the mouse model of streptozotocin (STZ)-induced pancreatic beta-cell ablation and diabetes was used as a model of placental pathology to investigate whether placental ECM influenced the expression of genes associated with different trophoblast sub-types. mTS cells were cultured on individual ECM components and qPCR analysis revealed that laminin promoted the expression of markers associated with undifferentiated TS cells, fibronectin promoted gene expression associated with syncytiotrophoblast (SynT) layer II cells and collagen IV promoted differentiation primarily to junctional zone trophoblast. Female mice administered STZ (blood glucose 300 mg/dL) or control (blood glucose 150 mg/dL) were mated. Placental pathology at embryonic day (E)14.5 was confirmed with reduced fetal blood space area, reduced expression of the pericyte marker SMA, and decreased expression of ECM proteins. mTS cells cultured on ECM isolated from STZ placenta were associated with reduced expression of undifferentiated mTS markers and SynA (SynT layer I), while expression of Tpbpa (junctional zone) was increased, suggesting that analysis of ECM isolated from the placenta may prove a useful tool in understanding trophoblast contribution to placental pathology.