Defining cellular diversity at the swine maternal-fetal interface using spatial transcriptomics and organoids.

Area of Science:

• Reproductive Biology
• Developmental Biology
• Comparative Mammalian Anatomy

Background:

• The placenta is crucial for mammalian fetal development, exhibiting diverse structures across species due to evolution.
• Porcine trophoblast heterogeneity in vivo poses challenges for studying placental development, lacking adequate in vitro models.
• Understanding placental development is key to fetal health and evolutionary biology.

Purpose of the Study:

• To develop an in vitro model that recapitulates the cellular heterogeneity of the porcine placenta.
• To identify conserved trophoblast populations and placental structures using integrated transcriptomic analysis.
• To provide a valuable tool for advancing research in placentation, evolution, and health.

Main Methods:

• Derivation of swine trophoblast organoids (sTOs) from full-term porcine placentas.
• Integration of Visium spatial transcriptomics from porcine placentas with single-cell transcriptomics from sTOs.
• Identification of novel placental markers and conserved cell communication programs.

Main Results:

• Swine trophoblast organoids (sTOs) successfully retained key transcriptional signatures of in vivo trophoblasts.
• Spatial transcriptomics identified novel markers, enabling precise separation of uterine and placental histological structures.
• Integrated transcriptomics revealed that sTOs spontaneously differentiate into conserved trophoblast populations with similar gene expression and communication programs.

Conclusions:

• Swine trophoblast organoids (sTOs) serve as a powerful and representative in vitro model for studying porcine placental development.
• The study provides a spatially resolved transcriptomic dataset of the maternal-fetal interface, facilitating future discoveries.
• This research advances understanding of placental development, evolution, and health across mammalian species.