Cellular Complexity of Hemochorial Placenta: Stem Cell Populations, Insights from scRNA-seq, and SARS-CoV-2 Susceptibility

Abstract

Purpose of Review The placenta is a transient organ that forms de novo and serves a critical role in supporting fetal growth and development. Placental oxygen, nutrients, and waste are transported through processes that depend on vascular structure and cell type-specific expression and localization of membrane transporters. Understanding how the placenta develops holds great significance for maternal–fetal medicine. The purpose of this review is to examine current information regarding placental progenitor populations. Recent Findings Recent advancements in single-cell RNA sequencing (scRNA-seq) provide unprecedented depth for the investigation of cell type-specific gene expression patterns in the placenta. Thus far, several mouse placenta scRNA-seq studies have been conducted which produced and analyzed transcriptomes of placental progenitors and cells of the fully developed placenta between embryonic day (E) 7.0 and E12.5. Together with human placenta scRNA-seq data which, in part, has been produced through coordinated research campaigns in the scientific community to understand the potential for SARS-CoV-2 infection, these mammalian studies lend fundamental insight into the cellular and molecular composition of hemochorial placentae found in both mouse and human. Summary Single-cell placenta research has advanced understanding of tissue-resident stem cells and molecules that are poised to support maternal–fetal communication and nutrient transport. Herein, we provide context for these recent findings by reviewing placental anatomy and cell populations, and discuss recent scRNA-seq mouse placenta findings. Further research is needed to evaluate the utility of placental stem cells in the development of new therapeutic approaches for the treatment of wound healing and disease.

Genome-wide identification of transcriptional enhancers during human placental development and association with function, differentiation, and disease

“…In this regard, a number of studies using microarrays [13][14][15][16], bulk RNA-seq [17][18][19], and single cell RNA-seq (scRNA-seq) [20][21][22][23][24][25][26][27] have examined aspects of how gene expression in the placenta changes over time in normal or pathologic pregnancies [10,12,28]. A number of studies have focused on differences in gene expression in placenta tissue in response to disease [12,22,[27][28][29][30][31][32][33], while others have used genomic profiling to define distinct cell types in the placenta [10,11,21,[33][34][35][36][37]. Fewer studies, however, have examined how diverse genomic features [e.g., transcription, histone modification, DNA methylation, transcription factor (TF) binding, chromatin accessibility, and chromatin interactions] change over the course of normal development.…”