Transcriptomic Profiling of Human Placenta in Gestational Diabetes
Mellitus at the Single-Cell Level
Abstract
Objective To generate a comprehensive transcriptomic profile of cellular
signifures and transcriptomes of human placenta in GDM by single-cell
RNA-sequencing (scRNA-seq), and built a comprehensive cell atlas. We
hope to reveal the molecular mechanism of pregnancy risk for GDM women.
Design Scientific study. Setting University Hospital and laboratories.
Population or Sample Pregnant women Methods 20 GDM women and 20 normal
pregnant women were recruited in present study. ScRNA-seq were loaded on
the Chromium Single Cell Controller Instrument (10×Genomics) to generate
single cell gel beads in emulsions (GEMs). Results A total of 27,220
cells from placenta samples were obtained. First, with the
cell-type-specific marker genes, we annotated 15 cell clusters into more
than 9 different cell types. Second, beside the classcial markers, we
also found some novel markers for distinguishing three kinds of
trophoblast and subtypes, which cloud be confirmed by
immunohistochemistry imaging. Third, we demonstrated the specific
placental function in GDM by the bioinformatics analysis of
differentially expressed genes, such as estrogen signaling pathway,
natural killer cell mediated cytotoxicity down- regulated. Fourth, there
are abundant ligand-receptor interactions between trophoblast and immune
cells in the maternal fetal interface microenvironment, such as
VEGFB-FLT1, MIF-EGFR, RPS19-C5AR1, SPP1-CD44These dysfunctional
ligand-receptor interactions may play the important roles in the
development of GDM. Conclusion This study provided the first
cell-type-specific transcriptomic alterations GDM placenta from single
cell level, exploded the cell identities and cell-type-specific marker
genes in the human placenta. In addition, it demonstrated the features
of placental function and cell interactions for GDM.