Citation: Erkenbrack, E. M., & Davidson, E. H. (2015). Evolutionary rewiring of gene regulatory network linkages at divergence of the echinoid subclasses.Proceedings of the National Academy of Sciences, 112(30), E4075-E4084.
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.
Cell type phylogenetics informs the evolutionary origin of echinoderm larval skeletogenic cell identity
To inform the evolution of the echinoderm larval skeletogenic cell, we have presented a framework for cell-type phylogenetic analysis that integrates spatial gene expression data with phylogenetic comparative methods to reconstruct ancestral gene expression. The genes we chose to include in our analyses have been studied in numerous echinoderm taxa and occupy crucial nodes of a well characterized gene regulatory network11,35. As the number of model and nonmodel organisms increases in evolutionary developmental biology, comparative analyses of spatial data will depend more on ancestral state reconstructions than on direct comparisons with an outgroup. However, it should be noted that such analyses are limited by several factors, including knowledge of a detailed GRN, invoking interspecies comparisons of development, and obtaining reliable divergence times and phylogenetic trees. The present study is not exempt from these limitations. Indeed, we chose to analyze five genes with broad phylogenetic sampling over twelve taxa. To support our findings, we ran pruned sensitivity analyses and concluded that decreasing the number of taxa reduced our ability to resolve ancestral states with confidence at certain nodes, especially the Asterozoan and Eleutherozoan MRCAs (Supplementary Fig. 12). Therefore, broad phylogenetic sampling is vitally important to resolve ancestral gene expression patterns. One could argue that increasing the number of genes in the analysis would help resolve the question of interest. However, we suggest that whether or not this is true will depend on the case at hand. For instance, in this study we analyzed genes from a GRN where the functional importance of many regulatory genes is well-known. In most cases, a well characterized GRN will not be available, and it will be equally important to possess a broad sampling of taxa across a phylogeny. For instance, as gene expression in early development becomes available in more asterozoans, which are under-sampled with respect to echinozoans in our analyses, we will gain greater confidence in our inferences at the asterozoan and eleutherozoan MRCAs. Indeed, we also see potential for the approach utilized herein to analyze ancestral states of GRN regulatory architecture. For example, the isolation and characterization of homologous cis-regulatory modules, from ATAC-seq, ChIP-seq, and other omics-level endeavors in phylogenetically distant organisms, could be then incorporated with the method presented here to determine which modules are lineage or cell-type specific.
© 2016 Eric M Erkenbrack and PNAS. All rights reserved.