Stress and Cell Type Origination


Günter P. Wagner

Alison Richard Professor of Ecology and Evolutionary Biology
Yale Systems Biology Institute
Department of Obstetrics, Gynecology and Reproductive Sciences
Yale University 


The origin of novel cell types is a major mode of the evolution of complex body plans in animals and plants. In this short talk I will report recent results about the evolutionary and developmental origin of a cell type only found in placental mammas, the decidual stromal cell (DSC) of the uterus. I will present comparative and experimental evidence suggesting a model where the process of DSC differentiation evolved from a wound induced fibroblast activation (WIFA). After wounding the fibroblasts around the wound undergo a transformation called “fibroblast activation” caused by TGFb1 signals from the injured epithelium. The activated fibroblasts and turn into so-called myofibroblasts. We argue that, ancestrally, the wound to the epithelium of the uterus caused by the embryo during attachment, led to a activation reaction in the endometrial stromal fibroblasts underlying the uterine epithelium. It was then the evolutionary modification of these activated endometrial fibroblasts that led to a novel cell type, the DSC, specifically dedicated to regulating the fetal-maternal relationship. This model is supported by single cell sequencing data that shows that the cells undergoing decidualization have substantial similarities to myofibroblasts before they differentiate into mature DSC. We also show that the FB activating signals TGFb1 plays a role in the differentiation of human ESF further emphasizing the affinity between decidualization and WIFA. This scenario fits well into a broader pattern of cell and tissue type origination related to cellular stress reactions, i.e. stress induced evolutionary innovation.