Single nuclei RNA-seq of mouse placental labyrinth development.

Bryan Marsh,Robert Blelloch

doi:10.7554/elife.60266

Abstract

The placenta is the interface between mother and fetus in all eutherian species. However, our understanding of this essential organ remains incomplete. A substantial challenge has been the syncytial cells of the placenta, which have made dissociation and independent evaluation of the different cell types of this organ difficult. Here, we address questions concerning the ontogeny, specification, and function of the cell types of a representative hemochorial placenta by performing single nuclei RNA sequencing (snRNA-seq) at multiple stages of mouse embryonic development focusing on the exchange interface, the labyrinth. Timepoints extended from progenitor-driven expansion through terminal differentiation. Analysis by snRNA-seq identified transcript profiles and inferred functions, cell trajectories, signaling interactions, and transcriptional drivers of all but the most highly polyploid cell types of the placenta. These data profile placental development at an unprecedented resolution, provide insights into differentiation and function across time, and provide a resource for future study.

Highlights

The placenta links maternal tissues and the embryo, providing necessary support and instructing the development of the embryo
The mouse placenta is separated into three main regions – the decidua, the junctional zone (JZ), and the labyrinth
Isolated nuclei were subjected to droplet-based sequencing using the 10x Genomics platform

Summary

Introduction

The placenta links maternal tissues and the embryo, providing necessary support and instructing the development of the embryo. The gas exchange interface in the mouse contains three layers of differentiated trophoblast separating maternal blood from the endothelial cells of the fetal vasculature (Simmons et al, 2008a; Maltepe and Fisher, 2015; Coan et al, 2005). Single-cell RNA sequencing has become the preferred method for understanding the composition of a complex tissue at the transcriptional level Several studies in both mouse (Nelson et al, 2016; Home and Ghosh, 2019) and human (Vento-Tormo et al, 2018; Suryawanshi et al, 2018) have profiled the placenta using scRNA-seq, syncytiotrophoblast are greatly underrepresented in these data. By separating and characterizing placental cell types, those in the labyrinth, these data provide a resource for understanding development in vivo, generation of molecular tools in vitro and in vivo, and for future modeling of prenatal pathologies

Results

Discussion

Materials and methods