How does a tissue-sized cell support pregnancy?

Abstract Authors: Madeline Keenan, Veronica Farmer, Yuan Wang, Amy S. Gladfelter
Department of Cell Biology and Biomedical Engineering, Duke University, Durham, NC 27710

Abstract Text:

The multinucleated syncytiotrophoblast (STB) is a tissue-sized single cell that separates the maternal and fetal vasculature during pregnancy. The STB wraps around the placenta villous trees, encasing them in a single cell with billions of nuclei in a common cytoplasm. This giant cell facilitates the exchange of nutrients, is essential for fetal immunoprotection, is the primary producer of pregnancy hormones, and performs critical metabolic roles. Further, the STB must simultaneously respond to gradients in oxygen, nutrients, maternal hormones, and pathogens that fluctuate in space and time. How does a single cell support these diverse homeostatic tasks and simultaneously respond to local cues and stresses? In recent work, we applied single-nucleus RNA sequencing and found that individual nuclei within the STB have distinct transcriptional programs despite all sharing the same cell cytoplasm. This indicates that STB nuclei are heterogeneous in activity and function. Nuclear individuality in transcription could both facilitate the myriad of STB functions and the insulation of the stress response to specific locations.  Our current work addressing how different nuclear identities are spatially patterned throughout the tissue, how nuclear identities arise mechanistically, and the functional consequences of nuclear heterogeneity in health and disease will be discussed.