Shared and Distinct Placental Immune Dynamics Across Pregnancy Complications

Paola Lopez Zapana * – Massachusetts Institute of Technology, Harvard Medical School; Daehee Han – Massachusetts General Hospital, Harvard Medical School; Courtney Ambrose – Massachusetts General Hospital, Broad Institute; Roya Best – Massachusetts General Hospital, Broad Institute; Zhaojing Liu – Massachusetts General Hospital; Elizabeth Tuttle – Massachusetts General Hospital, Broad Institute; Christopher Stueber – Massachusetts General Hospital, Broad Institute; Olyvia Jasset – Massachusetts General Hospital; Laura Ibanez-Pintor – Massachusetts General Hospital; Lydia Shook – Massachusetts General Hospital, Harvard Medical School; Douglas Lauffenburger – Massachusetts Institute of Technology; Alexandra-Chloé Villani † – Massachusetts General Hospital, Broad Institute, Harvard Medical School; Andrea Edlow † – Massachusetts General Hospital, Harvard Medical School

Abstract Text: The placenta is the heart of the maternal-fetal interface and is composed of cells that allow flow of oxygen and nutrients between mother and fetus while maintaining immune tolerance. High-dimensional techniques have been applied to understand placental cellular dynamics in individual pregnancy complications, but a comprehensive map of the maternal-fetal interface across all immune-mediated pregnancy complications has never been constructed. Understanding the complex cellular dynamics that govern tolerance (or lack thereof) and other critical biology at the maternal-fetal interface in healthy and complicated pregnancy is key to developing effective diagnostic and therapeutic strategies. To this end we collected 69 placenta samples from patients with a healthy pregnancy (labored n=9, unlabored n=13) as well as patients with pregnancy complications including spontaneous preterm birth (n=10), fetal growth restriction (n=9), pre-term preeclampsia (n=10), term preeclampsia (n=8) and type 1 diabetes (n=10). Male and female fetal sex were balanced across groups, to permit evaluation of sex differences on placental cellular programs. We profiled all samples by multi-modal single cell sequencing including gene expression, surface protein (CITE-seq) and paired single cell T cell receptor sequencing. We profiled over one million placental cells, creating the largest placenta single cell atlas to date. We identified various cellular lineages by unsupervised clustering. We characterized cellular programs, cell abundance changes and cell-cell communications, identifying the features that are shared and different across different pregnancy complications. This unprecedented biological and computational resource is urgently needed to guide evidence-based diagnostics and therapeutics that can improve maternal and fetal health.