March 16, 2022

Single-cell atlas of uterus generated at WSU/PRB holds potential for non-invasive pregnancy monitoring

A team of researchers at the Wayne State University School of Medicine and the National Institutes of Health’s Perinatology Research Branch in Detroit utilized single-cell RNA-sequencing together with cutting-edge analytical approaches to establish a single-cell atlas of the human uterus that holds promise of a potential means of non-invasively monitoring pregnancy and its complications.

The common pathway of delivery is largely orchestrated by intrauterine cellular and molecular processes, most of which are still poorly understood, the research team said. To fill this gap in knowledge, the researchers generated a single-cell atlas of the lower uterine segment at term by performing single-cell RNA-sequencing in tissue samples collected from 24 laboring and non-laboring women. The results, published in JCI Insight in “A single-cell atlas of the myometrium in human parturition,” https://insight.jci.org/articles/view/153921was the deep characterization of the cell type-specific transcriptomic activity as well as the cell-to-cell communications modulated during spontaneous labor at term. The research provides what may be the first demonstration that single-cell signatures derived from uterine tissues have potential predictive value for pregnancy disease and for monitoring labor status.

“Collectively, these data indicate that single-cell signatures derived from the myometrial tissues can be utilized for the temporal tracking of maternal systemic cellular dynamics throughout gestation, can identify cell type-specific transcripts that are enriched during the physiological process of labor, and may potentially serve as biomarkers,” said Nardhy Gomez-Lopez, Ph.D., associate professor of the WSU Department of Obstetrics and Gynecology, and section head of the Maternal-Fetal Immunobiology Unit of the Perinatology Research Branch. Dr. Gomez-Lopez; Roberto Romero, M.D., D.Med.Sci., chief of the Perinatology Research Branch, based at the Wayne State University School of Medicine, and professor of Molecular Obstetrics and Genetics at the WSU School of Medicine; and Roger Pique-Regi, Ph.D., associate professor of the Center for Molecular Medicine and Genetics and of the Department of Obstetrics and Gynecology, were co-senior investigators of this study and are the corresponding authors of the manuscript.

The data developed in the study show that the process of labor impacts the gene expression of non-immune and immune cell types in the smooth muscle tissue of the human uterus, and that several signaling pathways are governed by distinct cell types. These findings support the concept that immune cell-derived inflammation is a central component of human labor and provide novel evidence that uterine non-immune cells can also participate in the process.

View a video describing the study and findings here

Members of the research team include:

Valeria Garcia-Flores, Ph.D., M.Sc., assistant professor of Obstetrics and Gynecology, Maternal-Fetal Immunobiology Unit/Maternal-Fetal Single-Cell Genomics Unit, Perinatology Research Branch/NICHD
Azam Peyvandipour, Ph.D., postdoctoral fellow, Obstetrics and Gynecology, Center for Molecular Medicine and Genetics, Maternal-Fetal Single-Cell Genomics Unit, Perinatology Research Branch/NICHD
Adi Tarca, Ph.D., professor of Obstetrics and Gynecology, Bioinformatics and Computational Biology Unit, Perinatology Research Branch/NICHD, and adjunct professor of Computer Science
Errile Pusod, M.Sc., research assistant, Obstetrics and Gynecology, Maternal-Fetal Immunobiology Unit/Maternal-Fetal Single-Cell Genomics Unit, Perinatology Research Branch/NICHD 
Jose Galaz, M.D., assistant professor of Obstetrics and Gynecology, Maternal-Fetal Immunobiology Unit, Perinatology Research Branch/NICHD
Derek Miller, M.Sc., research associate, Obstetrics and Gynecology, Maternal-Fetal Immunobiology Unit, Perinatology Research Branch/NICHD
Gaurav Bhatti, M.Sc., research assistant, Obstetrics and Gynecology, Bioinformatics and Computational Biology Unit, Perinatology Research Branch/NICHD
Robert Para, M.D., Maternal-Fetal Medicine fellow, Perinatology Research Branch/NICHD
Tomi Kanninen, M.D., Maternal-Fetal Medicine fellow, Perinatology Research Branch/NICHD
Ola Hadaya, M.D., Maternal-Fetal Medicine fellow, Perinatology Research Branch/NICHD
Carmen Paredes, M.D., Maternal-Fetal Medicine fellow, Perinatology Research Branch/NICHD
Kenichiro Motomura, M.D., Ph.D., adjunct assistant professor, Obstetrics and Gynecology, Maternal-Fetal Immunobiology Unit, Perinatology Research Branch/NICHD
Jeffrey Johnson, M.D., associate professor, Obstetrics and Gynecology
Eunjung Jung, M.D., assistant professor, Obstetrics and Gynecology, Perinatology Research Branch/NICHD
Chaur-Dong Hsu, M.D., M.P.H., adjunct professor, Obstetrics and Gynecology, Perinatology Research Branch/NICHD 
Stanley Berry, M.D., professor and chair, Obstetrics and Gynecology, Perinatology Research Branch/NICHD

Subscribe to Today@Wayne

Direct to your inbox 3 times a week