Environmental factor – May 2022: Mapping cell communication in mouse uterus sheds light on pregnancy
Working together, several NIEHS units have launched a multi-technique study that allows researchers to not only profile gene expression patterns, but also learn where cells are located. Previous studies have not been able to determine location and therefore have not been able to map cell-to-cell communication as accurately.
Scientists from the Pregnancy and Female Reproduction Group, led by Francesco DeMayo, Ph.D., combined single-cell RNA sequencing assays (analytical procedures) with spatial transcriptomics, a technique that measures and maps the activity of genes in a tissue sample.
These two techniques allowed the researchers to identify 11 distinct compartments in mouse uteri, some of which had never been reported before – the mother-fetus interface and the transitional decidual zones. They were also able to establish the unique genetic signatures and predict the cellular composition and cellular interactions of all uterine compartments.
Their findings were published on March 31 in the journal Reproductive Biology.
Led by Intramural Research Training Fellow (IRTA) Rong Li, Ph.D., the group partnered with the institute’s Integrative Bioinformatics Support Group and Epigenetics Laboratory and stem cell biology.
“Our spatial transcriptomic results provide fundamental insight into uterine functions in early pregnancy,” Li said. how immune cells stimulate the remodeling of maternal vessels.”
Fine resolution, finer collaboration
To support embryo development, the uterus undergoes a series of complex spatio-temporal changes in early pregnancy. Previous studies that used traditional approaches such as histology predicted the existence of certain distinct mouse uterine compartments in early pregnancy. However, due to technical limitations, a systematic analysis of the specific transcriptome of the uterine compartment in early pregnancy has never been performed.
The group used 10x Genomics spatial transcriptomics technology because of its fine resolution at the level of a small cluster of multiple cells. Collaborative efforts included sample preparation by Li, sequencing by Xin Xu, Ph.D., of the Epigenomics and DNA Sequencing Core Laboratory, and data analysis and interpretation by Tian-Yuan Wang, Ph. D., of the Integrative Bioinformatics Support Group. .
“For us, the collaboration of the epigenetic core and the bioinformatics groups is like giving us a pair of magic glasses that can look through the gross morphology and peek into the delicate molecular world,” Li said.
The study was so effective that other NIEHS members are using the technique.
“In the year since the successful execution of the first case in March 2021, six NIEHS groups have used or planned to adopt the test in nine projects,” said Steve Wu, Ph.D., staff scientist of the NIEHS. “Such high demand shows the impact of implementing a test that facilitates intramural research and ensures the NIEHS is at the forefront of scientific efforts.”
Quote: Li R, Wang TY, Xu X, Emery O, Yi M, Wu SP, DeMayo FJ. 2022. Spatial transcriptomic profiles of mouse uterine microenvironments at pregnancy day 7.5. Biol Reprod; doi:10.1093/biolre/ioac061 [Online 31 March 2022].
(Kelley Christensen is a writer and contract writer for the NIEHS Office of Communications and Public Liaison.)