Neighbor-specific gene expression revealed from physically interacting cells during mouse embryonic development

Abstract

ABSTRACTCells continuously communicate with the neighboring cells during development. Direct interaction of different cell types can induce molecular signals dictating lineage specification and cell fate decisions. The current single cell RNAseq (scRNAseq) technology cannot study cell contact dependent gene expression due to the loss of spatial information. To overcome this issue and determine cell contact specific gene expression during embryogenesis, we performed RNA sequencing of physically interacting cells (PICseq) and assessed alongside our single cell transcriptomes (scRNAseq) derived from developing mouse embryos between embryonic day (E) 7.5 and E9.5. Analysis of PICseq data identifies an interesting suite of gene expression signatures depending on neighboring cell types. For instance, neural progenitor (NP) cells expressed Nkx2-1 when interacting with definitive endoderm (DE) and DE cells expressed Gsc when interacting with NP. Based on the identified cell contact specific genes, we devised a means to predict the neighboring cell types from individual cell transcriptome. We further developed spatial-tSNE to show the pseudo-spatial distribution of cells in a 2-dimensional space. In sum, we suggest an approach to study contact specific gene regulation during embryogenesis.