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

Area of Science:

• Developmental Biology
• Genomics
• Cell Biology

Background:

• Multicellular organism development relies on cell-cell communication.
• Single-cell RNA sequencing (scRNA-seq) lacks spatial information crucial for studying contact-dependent gene expression.
• Understanding direct cell-cell interactions is key to lineage specification and cell fate decisions.

Purpose of the Study:

• To develop and apply a novel method for analyzing gene expression in physically interacting cells during embryogenesis.
• To identify gene expression signatures dependent on specific neighboring cell types.
• To computationally predict and experimentally validate the impact of cell-cell contact on gene regulation.

Main Methods:

• RNA sequencing of physically interacting cells (PIC-seq) was performed on mouse embryos (E7.5-E9.5).
• PIC-seq data was analyzed alongside scRNA-seq data.
• Computational predictions of cell-cell contact effects were experimentally validated.
• A spatial-t-distributed stochastic neighboring embedding technique was developed for visualizing cell distribution.

Main Results:

• PIC-seq identified gene expression signatures specific to cell-cell contact.
• Neural progenitor (NP) cells upregulate Lhx5 and Nkx2-1 when interacting with definitive endoderm (DE) cells.
• DE cells upregulate Rax and Gsc when interacting with NP cells.
• A computational method was developed to predict the impact of neighboring cell types on gene expression.

Conclusions:

• PIC-seq is an innovative approach to study contact-specific gene regulation during embryogenesis.
• Direct cell-cell interactions significantly influence gene expression patterns in developing tissues.
• This study provides new insights into the molecular mechanisms governing cell fate decisions in developing embryos.