Submitted by T. Smyth on Thu, 09/01/2025 - 09:34
Professor Steve Charnock-Jones and Loke CTR collaborators have published their new work: "Single-cell RNA sequencing unveils CXADR as a critical regulator of the placental exchange surface" this week in Nature Communications.
Using single-cell RNA sequencing of mouse trophoblast stem cells they identify Nicol1 as a gatekeeper of the stem cell state. They also show that CXADR regulates the differentiation dynamics between the two syncytial layers of the mouse placenta.
The placenta is the critical interface between mother and fetus, and consequently, placental dysfunction underlies many pregnancy complications. The formation of the placenta requires expansion of trophoblast stem and progenitor cells followed by finely tuned lineage specification. Using single-cell RNA sequencing and CRISPR mediated gene knockout in mouse trophoblast stem cells the team identify a novel gatekeeper of the stem cell state - Nicol1. The mouse placenta has two distinct zones – the junctional zone (which has endocrine and storage functions) and the labyrinthine zone (for exchange of oxygen and nutrients between maternal and fetal circulations). They show that junctional zone precursors and precursors of one of the two syncytial layers of the mouse placental labyrinth, the syncytiotrophoblast-I lineage, initially share similar trajectories. They identify a lineage precursor marker (CXADR) and demonstrate that this cell surface protein regulates the differentiation dynamics between the two syncytial layers of the mouse labyrinth, ensuring the correct establishment of the placental exchange surface. Deciphering the mechanisms underlying trophoblast lineage specification will inform our understanding of human pregnancy in health and disease.
The paper is now available on Nature Communications Single-cell RNA sequencing identifies CXADRas a fate determinant of the placental exchange surface