Evolution of novel cell types during mammalian pregnancy
We have isolated and are culturing endometrial stromal fibroblasts cells (ESFs) from the uterus of the opossum Monodelphis domestica, called MdESFs. We conduct comparative analyses of this cell type with distantly-related ESFs from placental mammals to determine what makes each cell type tick. One goal is to reconstruct the ancestral cell type from which these modern cell types descend to help us understand how cell types are rewired and how new cells types arise during evolution.
Humans also have endometrial stromal fibroblasts (HsESFs) in the uterus. These HsESFs differentiate into a specialized cell called decidual stromal cells (HsDSCs). We differentiate HsESFs in petri dishes by adding the molecules cyclic AMP (8-Bromo-cAMP) and the hormone progesterone. In a recently submitted preprint, we show that opossum ESFs undergo a rapid stress response when cAMP and progesterone are added to their growth media.
Access the preprint here: bioRxiv
Erkenbrack EM, Maziarz JD, Griffith OW, Liang C, Chavan AR, Wagner GP: The mammalian decidual cell evolved from a cellular stress response. bioRxiv preprint available.
Gene regulatory networks directing a terminal cell fate decision in humans
In preparation for implantation of the embryo, the lining of the human uterus swells and HsESFs, which inhabit the uterus, undergo morphological and functional changes, becoming plump and round glycogen-filled decidual stromal cells (HsDSCs). We are trying to understand how the genes are interconnected into networks of regulatory systems that work to control this process. These types of interdependent relationships in the cell where genes control other genes are called gene regulatory networks (GRNs). We are trying to disentangle the GRN that driving the conversion of HsESFs into HsDSCs in the human uterus.
While this project description may seem far from human reproductive health, actually it is not. This network of genes is critical for implantation of the embryo into the lining of the uterus. It also has a say in how well the embryo can invade into the uterus, resulting in nutrition and resources for the fetus. Understanding how these genes are wired together to control this reaction has the potential to inform decisions for pregnant women or those trying to become pregnant.