New cell atlas reveals biological correlates of pregnancy complications

The biological connection between a pregnant woman and her developing baby has been mapped in unprecedented detail by UC San Francisco scientists, revealing new cell types and providing insight into conditions such as preeclampsia, premature birth and miscarriage.

Using advanced single-cell and spatial tools, the researchers analyzed approximately 200,000 individual cells and compared them to approximately 1 million cells in their native state within uterine and placental tissue. This helped them identify different types of cells, track their development, and see how they are linked to pregnancy complications.

“This work gives us a clearer picture than ever before of this important area,” said Jingjing Li, PhD, associate professor in UCSF’s Department of Neurology and the Eli and Edith Broad Center of Regenerative Medicine and Stem Cell Research. is the senior author of the study published in Nature On 8th April.

The maternal-fetal interface is a temporary but essential structure composed of uterine and placental cells that forms approximately one week after fertilization and persists throughout pregnancy. It aids in the development of the fetus while maintaining the health of the mother. Its complexity has long limited the ability of scientists to study how healthy pregnancies develop and why complications arise.

“By examining this tissue cell by cell during pregnancy, we can begin to understand both normal development and what can go wrong.”

Susan J. Fisher, PhD, professor of obstetrics, gynecology and reproductive sciences at UCSF and co-leader of the study

discovery of a new cell type

The atlas revealed a previously unknown maternal cell type, where fetal placental cells first enter the uterus. These cells appear to control how deeply placental cells invade the uterine tissue, a process that is essential for establishing blood flow to the fetus.

Researchers found that these cells contain a cannabinoid receptor. Placental cell invasion was further restricted due to exposure to cannabinoid molecules.

“Population studies have linked cannabis use during pregnancy to poor outcomes,” said Cheng Wang, PhD, the study’s first author. “This cell type may help explain the biological basis of that relationship.”

To understand how the complications arise, the team integrated genetic data from more than 10,000 patients. They mapped genetic risk signals for conditions including premature birth, preeclampsia and miscarriage onto regulatory regions of DNA that control gene activity. This approach allowed researchers to identify the specific cell types and conditions most strongly associated with each condition.

The team then focused on preeclampsia, a potentially life-threatening disorder marked by sudden high blood pressure. They found that the most affected cell types are involved in remodeling the mother’s uterine blood vessels, a process necessary to supply adequate blood to the placenta. The findings suggest that preeclampsia may result from disrupted communication between maternal and fetal cells that normally coordinate this process.

After establishing a detailed map of healthy pregnancies, the researchers plan to study complicated pregnancies to identify potential targets for treatment.