Cells are constantly communicating with each other by releasing proteins and other biomolecules into their surroundings. This process, called secretion, is crucial for many biological functions—whether it’s sending signals to other cells, fighting off infections, or even delivering therapeutic drugs. However, scientists still don’t fully understand the gene activity that drives different secretion patterns in individual cells.

Researchers from the David Geffen School of Medicine at the University of California Los Angeles have developed an innovative technique called SEC-seq to bridge this knowledge gap. This method allows scientists to analyze both the secretions of a single cell and the genes that control them—at the same time.

A summary of the SEC-seq workflow

Cells are loaded into Nanovials, and their secretions are captured by attached antibodies. The secretion levels are quantified by using an oligo-barcoded secretion-detection antibody at a single-cell level and are linked to the transcriptomes of each cell through emulsification of the cell-loaded Nanovials into droplets by using standard single-cell sequencing workflows, forming single-cell GEMs (gel beads in emulsions). Ab, antibody; Sec., secretion.

How SEC-seq Works

SEC-seq uses tiny hydrogel beads, called Nanovials, to trap cells along with the molecules they release. Here’s a simplified breakdown of the process:

1. Capturing Secretions – Cells are placed onto Nanovials, where secreted proteins are tagged with special molecular barcodes.
2. Sorting Cells – Using flow cytometry, cells are separated based on how much of a particular protein they secrete.
3. RNA Sequencing – The sorted cells are analyzed with single-cell RNA sequencing (scRNA-seq) to link their gene activity to their secretory behavior.

Why this is Important

SEC-seq provides a powerful tool for studying how cells regulate secretion, which is critical for fields like immunology and regenerative medicine. The research team demonstrated its potential by:

• Tracking T cell receptor sequences alongside cytokine secretion to study immune responses.
• Identifying a highly secreting population of mesenchymal stromal cells with regenerative potential.
• Mapping plasma cell transcriptomes to immunoglobulin secretion levels.

This breakthrough could pave the way for engineering cells with enhanced therapeutic properties, leading to more effective cell-based therapies in the future.