Citation: Nnamani, M.C., Ganguly, S. , Erkenbrack, E.M., Lynch, V.J., Mizoue, L.S., Tong, Y., Darling, H.L., Fuxreiter, M., Meiler, J., Wagner, G.P. (2016). A derived allosteric switch underlies the evolution of conditional cooperativity between HOXA11 and FOXO1. Cell Reports, 15(10), P2097-2108.
Decidualization of Human Endometrial Stromal Fibroblasts is a Multiphasic Process Involving Distinct Transcriptional Programs
Decidual stromal cells differentiate from endometrial stromal fibroblasts (ESFs) under the influence of progesterone and cyclic adenosine monophosphate (cAMP) and are essential for implantation and the maintenance of pregnancy. They evolved in the stem lineage of placental (eutherian) mammals coincidental with the evolution of implantation. Here we use the well-established in vitro decidualization protocol to compare early (3 days) and late (8 days) gene transcription patterns in immortalized human ESF. We document extensive, dynamic changes in the early and late decidual cell transcriptomes. The data suggest the existence of an early signal transducer and activator of transcription (STAT) pathway dominated state and a later nuclear factor kB (NFKB) pathway regulated state. Transcription factor expression in both phases is characterized by putative or known progesterone receptor (PGR) target genes, suggesting that both phases are under progesterone control. Decidualization leads to proliferative quiescence, which is reversible by progesterone withdrawal after 3 days but to a lesser extent after 8 days of decidualization. In contrast, progesterone withdrawal induces cell death at comparable levels after short or long exposure to progestins and cAMP. We conclude that decidualization is characterized by a biphasic gene expression dynamic that likely corresponds to different phases in the establishment of the fetal–maternal interface.
Animals consist of a wide variety of cells that serve different functions depending on their location in the body. Cells with similar functions, or cell types, in different animal species are related both by an evolutionary line of descentÐsimilar to the relatedness of species themselvesÐand by a developmental line of descent in the embryo. Networks of interacting genes, or gene regulatory networks, control gene expression in the cell, thereby specifying cell type identity. Understanding how new cell types arise by changing gene regulatory networks is critical both to comprehending fundamental aspects of human biology and to manipulating cell types in the laboratory. We approached this question by studying endometrial stromal fibroblast (ESF) cells from the uterus of humans and opossums, two distantly related mammals. We showed that the distantly related cell type in opossum expresses a similar set of regulatory genes as the human cell, but in response to pregnancy-related signals, the opossum cells induce a stress response. In the human cells, these signals induce differentiation into decidual cells, a specialized cell type present in humans and closely related mammals. These results suggest that a gene regulatory network that modulated an ancestral, pregnancy-related stress response was hijacked and repurposed to function in differentiation and specification of the decidual cell type.
© 2016 Eric M Erkenbrack and Cell Press. All rights reserved.