An Isoform-resolved Single-cell Atlas of the Murine Placenta: Gestational Dynamics During Syngeneic and Semi-allogeneic Pregnancy

While single-cell studies defined placental cellular diversity, alternative splicing's contribution to immune regulation remains poorly understood. Here, we present an isoform-resolved single-cell transcriptomic resource of the murine placenta across mid- and late gestation in syngeneic and semi-allogeneic pregnancies.

We identify global suppression of cytokine networks during mid-gestation semi-allogeneic pregnancies, accompanied by erythroid populations co-expressing immune programs. Isoform-level analysis reveals the coordinated generation of alternatively spliced cytokine receptor variants, including soluble decoys and intracellular traps, lacking necessary signaling domains. These variants co-express with canonical receptors, decoupling ligand binding from downstream signal transduction to fine-tune immune responses.