Jian Shu, PhD, an investigator in the Cutaneous Biology Research Center at Massachusetts General Hospital and an Assistant Professor of Dermatology at Harvard Medical School, is senior author of a study in Nature Medicine, Spatial Multiomic Landscape of the Human Placenta at Molecular Resolution.
What Question Were You Investigating in this Study?
The placenta is tightly linked to a number of intrapartum and postpartum diseases, including but not limited to:
- Gestational hypertension and diabetes
- Maternal infection
- Preeclampsia and eclampsia
- Spontaneous pregnancy loss
- Hemorrhage
These pathologies contribute to the 30-60% of pregnancies that do not achieve offspring viability.
Prior pioneering human placenta studies have used genomics tools to profile the heterogeneous landscape of the maternal-fetal interface. Early studies were limited by factors including limited scale, low resolution, and the absence of multiomic datasets to link epigenetic regulation and gene expression or genomically profile cells in space.
What Were the Results?
To overcome these limitations, we generated by far the largest and most comprehensive spatially resolved single-cell census and molecular architecture of the first trimester human placenta.
In this manuscript, we performed paired scRNA-seq and scATAC-seq on the same cells with three complementary single-cell spatial multiomics profiling technologies: Slide-tags (spatial joint scRNA-seq and scATAC-seq), STARmap In Situ Sequencing (ISS) (1,001 genes), and STARmap In Situ Hybridization (ISH) (48-plex targeted gene panels).
By integrating single-cell multiomic data with spatial multiomic mapping data at molecular resolution, we successfully built a spatially resolved genome-wide multiomic atlas of the early placenta through multi-modal data integration and imputation.
The paper describes a first-of-its-kind spatial multiomic atlas derived from nearly 1 million cells of the first trimester human placenta at single-cell and molecular resolution.
We identified spatially resolved gene expression and CRE-linked epigenetic programs likely involved in continuous placental evolution and adaptation, including tumor invasion and immune evasion mechanisms.
We found that integrative approach allowed the complementary techniques to synergistically account for each of their respective limitations, enhancing the breadth of our mapping and the reliability of our dataset while striking a time and cost-effective balance between throughput and resolution.
What are the Clinical Implications and Next Steps?
This spatially resolved single-cell multiomic framework of the first trimester human placenta serves as a blueprint for future studies on early placental development and pregnancy, which will lead to better diagnosis and potential therapeutic solutions of placental dysfunctions in pregnancy.
