Citation: Kshitiz, Afzal, J., Maziarz, J.D., Hamizadeh, A., Liang, C., Erkenbrack, E. M., Nam, H., Haeger J., Pfarrer, C., Hoang, T., Ott, T., Spencer, T., Pavlicev, M., Antczak, D.F., Levchenko, A., Wagner G.P. (2019). Evolution of placental invasion and cancer metastasis are causally linked. Nature Ecology and Evolution (2019).
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.
Cells frequently counteract environmental stress by conserved molecular mechanisms, leading to stress mitigation or apoptosis. Increasingly, studies on cellular stress responses intersect with cell type differentiation programs. It is hypothesized that integration of these conserved pathways is a mechanism of stress‐induced evolutionary innovation that is capable of generating novel cell types.
© 2016 Eric M Erkenbrack and SpringerNature. All rights reserved.