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Scientists Create a Single-Cell Atlas of the Human Placenta During Labor

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During childbirth, numerous physiological and cellular transformations take place in both the mother and infant. Scientists have created a single-cell atlas of the human placenta during labor. The study, published in Science Translational Medicine, aims to unravel the intricate events occurring at the maternal-fetal interface.

Building a single-cell atlas

The act of spontaneous labor requires complex cellular signaling. However our understanding of these cellular processes during term labor, which is past 37 weeks, has been limited. In particular, the cross-talking interactions between maternal and fetal cells had not been fully elucidated, until now.

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Dr. Valeria Garcia-Flores, from Washington University School of Medicine in St. Louis, and colleagues are the first to produce a single-cell analysis of the human placenta and its surrounding membranes.

Understanding the cells that are most affected by labor

Garcia-Flores and the team used single-cell RNA-sequencing to track the activity and signaling patterns of different cell types in samples taken from 42 term pregnancies.

The cells that surround the fetus and rupture during childbirth – found in the chorioamniotic membranes – were found to experience the most changes in gene expression during labor. Cells involved in inflammatory signaling, including the fetal stromal and maternal decidual cells, were also particularly active at this time, producing signals that suggest inflammation may be essential towards sustaining labor.

Single-cell and bulk RNA-sequencing

Both single-cell and bulk RNA-sequencing are methods used to study gene expression profiles in cells. 

Bulk RNA-sequencing refers to techniques that measure the average gene expression across an entire population of heterogeneous cells. This is often a cheaper, quicker method to study gene expression patterns in different tissues and cell types.

Single-cell RNA-sequencing analyzes gene expression profiles in individual cells from homogenous and heterogenous populations. This method can provide a more detailed view when studying distinct cell populations that wouldn’t be revealed in bulk RNA-sequencing.

Identifying placental biomarkers

Garcia-Flores and colleagues combined their single-cell sequencing data with bulk RNA-sequencing datasets to classify cell-specific signatures of labor, which were detected in maternal blood samples from both pre-term and term pregnancies. The team demonstrated that, even early in gestation, these labor-specific placental signatures could be detected in women that were destined to undergo spontaneous preterm birth. This suggests that the signature could be used as a non-invasive biomarker to predict spontaneous labor in pre-term mothers.

Although further studies are needed to assess these biomarkers in a larger cohort, the study provides insight into the necessary communication that takes place at the maternal-fetal interface during labor and childbirth.


Reference: Garcia-Flores V, Romero R, Tarca AL, et al. Deciphering maternal-fetal cross-talk in the human placenta during parturition using single-cell RNA sequencing. Sci Transl Med. 2024;16(729):eadh8335. doi: 10.1126/scitranslmed.adh8335

This article is a rework of a press release issued by the National Institutes of Health. Material has been edited for length and content.