Citation: Rytkönen, K. T, Erkenbrack, E. M., Poutanen, M., Elo, L. L., Pavlicev, M., Wagner, G. P. (2018). Decidualization of Human Endometrial Stromal Fibroblasts is a Multiphasic Process Involving Distinct Transcriptional Programs. Reproductive Sciences, Online First.
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.
Conserved regulatory state expression controlled by divergent developmental gene regulatory networks in echinoids
Evolution of the animal body plan is driven by changes in developmental gene regulatory networks (GRNs), but how networks change to control novel developmental phenotypes remains in most cases unresolved. Here we address GRN evolution by comparing the endomesoderm GRN in two echinoid sea urchins, Strongylocentrotus purpuratus and Eucidaris tribuloides, with at least 268 million years of independent evolution. We first analyzed the expression of twelve transcription factors and signaling molecules of the S. purpuratus GRN in E. tribuloides embryos, showing that orthologous regulatory genes are expressed in corresponding endomesodermal cell fates in the two species. However, perturbation of regulatory genes revealed that important regulatory circuits of the S. purpuratus GRN are significantly different in E. tribuloides. Thus for instance mesodermal Delta/Notch signaling controls exclusion of alternative cell fates in E. tribuloides but controls mesoderm induction and activation of a positive feedback circuit in S. purpuratus. These results indicate that the architecture of the sea urchin endomesoderm GRN evolved by extensive gain and loss of regulatory interactions between a conserved set of regulatory factors that control endomesodermal cell fate specification.
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