Apr 10, 2026
3 min read
What causes preeclampsia and premature labor?One study mapped 1.2 million cells at the maternal-fetal interface.Discover new cell types that regulate placental growth and the biological effect of cannabis on pregnancy.
Summary: In a landmark study, scientists have created the most detailed map yet of the "maternal-fetal interface"—the critical biological boundary where the mother's uterus meets the baby's placenta.
By analyzing more than 1.2 million cells using single-cell and spatial techniques, the researchers discovered entirely new cell types and identified specific genetic "command centers" that malfunction in preeclampsia, miscarriage, and premature birth.This atlas provides a molecular blueprint that could lead to the first truly targeted therapies for pregnancy complications.
- Cannabis connection: Scientists have discovered a new type of maternal cell that regulates the attachment of the placenta to the uterus.These cells contain a cannabinoid receptor;exposed to cannabis particles reduce placental invasion and provide a biological explanation for why cannabis use is associated with poor pregnancy outcomes.
- Preeclampsia solved: Studies have found that preeclampsia - dangerous high blood pressure - is likely the result of a breakdown in the communication between the mother and the fetal cells that are supposed to 'renovate' the blood vessels in the uterus to increase blood flow.
- Big Data Scale: The team analyzed 200,000 individual cells and captured nearly a million more in their exact anatomical positions to determine exactly who "talked" to whom in the uterus.
- Risk mapping: By combining data from 10,000 patients, the team matched the genetic risk signals for preterm birth and miscarriage to specific cell types, going beyond general theories to identify the exact cellular culprits.
- Important Limits: The barrier between parent and child is a temporary body that is formed one week after fertilization.It is responsible for feeding the fetus and protecting the mother's immune system from damaging the child's "foreign" DNA.
The biological connection between a pregnant woman and her developing baby has been mapped in unprecedented detail by scientists at the University of San Francisco, revealing new cell types and insights into conditions such as preeclampsia, premature birth and miscarriage.
Using advanced single-cell and spatial tools, the researchers analyzed about 200,000 individual cells and compared them to about a million cells in their original locations in uterine and placental tissue.This allowed them to identify different types of cells, track how they develop and see how they are linked to pregnancy complications.
"This work gives us a much clearer picture of this critical region than before," said Jingjing Li, PhD, associate professor in UCSF's Department of Neurology and the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, and senior author of the study, which was published April 8 in Nature.
The mother-fetal interface is a temporary but necessary structure made up of cells from the uterus and placenta, which forms about a week after fertilization and lasts throughout pregnancy.It supports the development of the fetus and maintains the health of the mother.Its complexity has long limited researchers' ability to study how healthy pregnancies develop and why complications arise.
"By examining this tissue cell by cell during pregnancy, we can understand both normal development and what can go wrong," said Dr. Susan J.Fisher, professor of obstetrics, gynecology and reproductive sciences at UCSF and co-author of the study.
Discover a new cell type
The atlas revealed a previously unknown type of maternal cell, where cells from the fetal placenta first enter the uterus.These cells appear to regulate how deeply placental cells penetrate the uterine tissue, which is necessary to establish blood flow to the fetus.
The researchers discovered that these cells carry cannabinoid receptors. Exposure to cannabinoid molecules further limits the invasion of placental cells.
"Population studies have associated marijuana use during pregnancy with worse outcomes," said the study's first author, Cheng Wang, PhD."This cell type may help explain the biological basis of this association."
To understand how complications arise, the team combined genetic data from more than 10,000 patients.They mapped genetic risk signals for conditions including premature birth, preeclampsia and miscarriage to regulatory regions of DNA that control gene activity.This approach allowed the 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 disease characterized by sudden high blood pressure.They found that the most affected cell types are involved in the remodeling of the mother's uterine blood vessels, a process necessary to supply the placenta with enough blood.The results suggest that preeclampsia may be due to disrupted communication between maternal and fetal cells that normally coordinate this process.
After creating a detailed map of healthy pregnancies, the researchers plan to study complicated pregnancies to identify treatment targets.
Answered key questions:
A: Think of the placenta as the root of a tree if it does not "drill" deep into the mother's uterine tissue. It will not be able to effectively absorb into her bloodstream.The study found new specific cells that act as protectors for this process if these cells are too tight (because these cells are exposed to cannabinoids) the baby will not get the nutrients he needs.
Answer: Until now, we did not know which cells fail during miscarriage.By mapping genetic risk signals from 10,000 patients onto this new 3D atlas, doctors can now see which cell "states" are most vulnerable.This allows researchers to develop drugs that target specific cells to strengthen the bond between mother and baby.
Answer: We knew preeclampsia involved high blood pressure, but we didn't know it was a "communication" error.Studies show that maternal and fetal cells must "talk" to each other in order to dilate the mother's blood vessels.In preeclampsia, this communication is interrupted, and the vessels remain narrow, causing jumps in the mother's blood pressure and the baby's body trying to pump blood.
- This article was edited by the editors of Neuroscience News.
- The storyboard has been revised.
- Added additional information by our staff.
About this genetics and neurodevelopmental research news
Author: Laura Kurtzman
Contact: Laura Kurtzman - UCSF
Image: Image from Neuroscience News
Original Research: Closed Access.
Serena Tamura, Andrew D. Nelson, Perry W.E. Spratt, Elizabeth C. Hamada, Zhujia Zhu, Henry Qiang, Zhizheng Li, Colin Arnold, Vladsianana Berskin, Benzin, Benzining, Colin Arnold, Andrew D. Nelson, "Single-Temple of theHuman-Temporal Interface" Zhao, Stephanie S. Holden, Atehsa Sahagun, Carolyn M. Kishan, Kongyi Lu, Roy Ben-Shalom, Sunare E. Taloma, Celine Shamiloglu, Ing C. Lee, Lia Min, Paul M.Jenkins, Jane Q. Pan, Jane T.J.Paz, Jane T.J.Paz and St.Bender Nature
Single-cell spatiotemporal dissection of the human maternal-fetal interface
Most single-gene diagnosed neurodevelopmental disorders are caused by haploinsufficiency, in which only one of the two copies of the gene is functional.SCN2A haploinsufficiency is one of the most common causes of neurodevelopmental disorder, often presenting with autism spectrum disorder, intellectual disability, and, in a subset of children, refractory epilepsy.
Here, using SCN2A haploinsufficiency as a proof-of-concept, we show that correction of existing functional gene copies by CRISPR activation (CRISPRa) can rescue genetic phenotypes in Scn2a haploinsufficient mice.
We first demonstrate that restoration of Scn2a expression in heterozygous Scn2a-conditioned mice rescues electrical defects associated with Scn2a haploinsufficiency (Scn2a +/-).
Next, using CRISPRa-based adeno-associated virus therapy in adolescent mice, we show that intrinsic and synaptic defects in neocortical pyramidal cells, a key cell type implicated in the neurodevelopmental disorder and seizure etiology of SCN2A deficiency, can be corrected.
Furthermore, we found that systemic delivery of CRISPRa protected Scn2a +/- mice from chemoconvulsant-induced seizures.Finally, we also show that adeno-associated CRISPRa virus treatment rescues excitability in neurons protected by the human SCN2A haplotype.
Our results demonstrate the potential of this therapeutic approach to rescue SCN2A haploinsufficiency and suggest that rescue even at the adolescent stage can improve the neurodevelopmental phenotype.
