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

The maternal-fetal interface requires precise immune tolerance followed by coordinated inflammation at term. 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. At term, this landscape shifts to coordinated pro-inflammatory signaling. This interactive dataset provides a systems-level framework for understanding how post-transcriptional mechanisms shape immune adaptation during murine pregnancy.