Trophoblast paracrine signaling regulates placental hematoendothelial niche

Abstract

The placenta acts as a major organ for hematopoiesis. It is believed that placental hematopoietic stem and progenitor cells (HSPCs) migrate to the fetal liver to ensure optimum hematopoiesis in the developing embryo. The labyrinth vasculature in a mid-gestation mouse placenta provides a niche for the definitive hematopoietic stem cell (HSC) generation and expansion. It has been proposed that these processes are regulated by a host of paracrine factors secreted by trophoblast giant cells (TGCs) at the maternal-fetal interface. However, the molecular mechanism by which the TGCs regulate the hematoendothelial niche in a developing placenta is yet to be defined. Using a TGC-specific Gata2 and Gata3 double knockout mouse model, weshow that the loss of GATA2 and GATA3 at the TGC layer leads to fetal growth retardation and embryonic death due to disruptions in the delicate hematopoietic-angiogenic balance in the developing placenta. Using single-cell RNA-Seq analyses, we also show that the loss of GATA factors in the TGCs results in the loss of HSC population within the placental labyrinth and is associated with defective placental angiogenesis. Interestingly, we also found that this TGCspecific GATA factor-loss leads to impaired differentiation and distribution of trophoblast progenitor cells. Our study helps to define the GATA-dependent non-autonomous signaling mechanisms of the primary parietal trophoblast giant cells by which it regulates the delicate hematopoietic-angiogenic balance in the developing placenta.

Single nuclei RNA-seq of mouse placental labyrinth development

“…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, however, syncytiotrophoblast are greatly underrepresented in these data. Studies in mouse have either avoided profiling the labyrinth trophoblast, or are unable to distinguish between the two SynT layers ( Nelson et al, 2016 ; Home and Ghosh, 2019 ).…”

“…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, however, syncytiotrophoblast are greatly underrepresented in these data. Studies in mouse have either avoided profiling the labyrinth trophoblast, or are unable to distinguish between the two SynT layers ( Nelson et al, 2016 ; Home and Ghosh, 2019 ). Recently, application of droplet-based transcriptome profiling to nuclei has been shown to provide high quality data and results which recapitulate those from whole cell scRNA-seq ( Habib et al, 2017 ; Lake et al, 2018 ; Bakken et al, 2018 ; Ding et al, 2020 ).…”