The mammalian decidual cell evolved from a cellular stress response

Among animal species, cell types vary greatly in terms of number and kind. The broad range of number of cell types among species suggests that cell type origination is a significant source of evolutionary novelty. The molecular mechanisms giving rise to novel cell types, however, are poorly understood. Here we show that a novel cell type of eutherians mammals, the decidual stromal cell (DSC), evolved by rewiring an ancestral cellular stress response. We isolated the precursor cell type of DSCs, endometrial stromal fibroblasts (ESFs), from the opossum Monodelphis domestica. We show that, in opossum ESF, the majority of decidual core regulatory genes respond to decidualizing signals, but do not regulate decidual effector genes. Rather, in opossum ESF, decidual transcription factors function in apoptotic and oxidative stress response. We propose that the rewiring of cellular stress responses could be a general mechanism for the evolution of novel cell types. Examination of mRNA profiles of in vitro cultured opossum endometrial stromal fibroblasts and those exposed to: 1) eutherian differentiation media, containing cyclic AMP (cAMP) analogue 8-Br-cAMP and the progesterone (P4) analogue medroxyprogesterone acetate (MPA), 2) MPA, 3) PGE2, 4) PGE2 and MPA.