Placental gene expression-based cell type deconvolution: Cell proportions drive preeclampsia gene expression differences

The placenta mediates adverse pregnancy outcomes, including preeclampsia, characterized by gestational hypertension and proteinuria. Placental cell type heterogeneity in preeclampsia is not well-understood and limits mechanistic interpretation of bulk gene expression measures. We generated single-cell RNA-sequencing samples for integration with existing data to create the largest deconvolution reference of 19 fetal and 8 maternal cell types from placental villous tissue at term. We deconvoluted eight published microarray case-control studies of preeclampsia. Our findings indicate substantial placental cellular heterogeneity in preeclampsia that predict previously observed bulk gene expression differences. Our deconvolution reference lays the groundwork for cellular heterogeneity-aware investigation into placental dysfunction and adverse birth outcomes. Overall design: Five placentas were collected for study. Four placentas were dissociated for cell type sorting and bulk RNA-sequencing. Two placentas were dissociated for single-cell RNA-sequencing; each included a technical replicate. One placenta contributed data for both experiments.