Oral or Poster Presentation
Concurrent Session 4C - Reproductive Science
Introduction: Early establishment of the human placenta is a dynamic process that involves the differentiation of cells from the blastocyst’s trophectoderm into highly specialized placental cells called trophoblasts. Trophoblasts facilitate many placenta-related processes in pregnancy. Unfortunately, little is known about the cellular and molecular processes controlling progenitor cell differentiation into mature trophoblast subsets. Using a state-of-the-art single cell transcriptomic approach, we set out to define key cell trajectories and transcriptional programs important in early placental development.
Methods: cDNA libraries from >11,000 cells of early (n=4, 6 weeks’ gestational age) and late (n=3, 11 weeks’ gestational age) first trimester placentas were generated using the 10X Genomics Chromium platform. Following data normalization, cell clustering, cell lineage trajectory (pseudotime), and differential gene expression analyses were performed; FDR < 0.05.
Results: Trophoblasts comprised 43% of total placenta cells captured, and within these, 9 distinct clusters were identified in early first trimester samples, while 8 clusters were identified in late first trimester samples. In both early and late gestational timepoints, 6 villous trophoblast clusters were identified. Clusters representing syncytiotrophoblast progenitors and invasive extravillous subtypes were also present in early and late samples. However, the 6-week samples showed greater diversity with two syncytiotrophoblast and two extravillous trophoblast clusters compared with the 11-week samples which had only one syncytiotrophoblast and one extravillous trophoblast cluster. Pseudotime analysis ordered trophoblasts along two distinct cell differentiation trajectories: The villous trajectory and the extravillous trajectory. Pseudotime modelling also identified a primitive origin defined by unique gene signatures and pathways that together reveal a progenitor or stem cell state.
Conclusion: Our analyses identify multiple trophoblast states within the first trimester of pregnancy. Moreover, a transcription signature aligning with a primitive progenitor state reveals pathways and possible markers of trophoblast villous progenitors/stem cells. Together, this work sheds new insight into cellular processes in placental development.