New proteomics technology sheds light on health and disease

The brain of a rat in which a fluorescent protein has been used to highlight transplanted human brain cells – Copyright Stanford University/AFP Sergiu PASCA

A single molecule in just one of the body’s cells can reveal considerable information about a person’s health, according to Cedars-Sinai investigators.

Using a powerful technology termed single-cell proteomics, researchers are tracking proteins, cell by cell, in order to shed new light on how the human body works and how diseases develop.

Single-cell proteomics (SCP) is an advanced, high-sensitivity analytical approach designed to map protein expression, post-translational modifications, and protein-protein interactions within individual cells. By overcoming the averaging effect of bulk sample analysis, the technology enables the identification of hundreds to thousands of proteins in single cells.

Proteomics as a concept concerns the study of the complete set of proteins expressed by an organism since the molecules carry out nearly every bodily activity.

The challenge often facing scientists is that a typical laboratory sample of human tissue contains thousands of cells, and each cell is packed with multiple copies of thousands of different proteins.

To connect each protein to the correct cell, single-cell proteomics investigators rely on equipment called mass spectrometers. These machines use magnetic forces to separate proteins by their molecular weight or mass. Once the proteins are sorted, researchers can identify them and match them to the cells that contained them.

Cedars-Sinai investigators have uncovered new types of heart cells. These provide insights into the way arteries work.

The development of proteomics was pioneered by Jennifer Van Eyk, PhD, who helped foster the discipline. Van Eyk’s focus is with clinical proteomics, which applies scientific discoveries to patient care. At Cedars-Sinai, she directs the Smidt Heart Institute’s Advanced Clinical Biosystems Research Institute, which she founded in 2014 to foster collaboration among scientists, physicians and biotechnology companies.

One of Van Eyk’s most recent achievements was to co-lead a study revealing that cardiomyocytes, the muscle cells of the heart, are not all identical. Van Eyk tracked protein changes in individual cells as they developed from stem cells into heart cells, and revealed important differences in the structure and metabolism of these cells as compared with naturally occurring heart cells. While single-cell RNA methods are widely available now and allow thousands of genes to be assessed simultaneously, there is very little data looking at the inventory of proteins within single cells simultaneously. 

Through single-cell proteomics, she and her colleagues discovered two new hybrids of cardiomyocytes that produce both heart- and neuron-related proteins. Her team is now exploring whether gender differences in cardiomyocytes could affect how a person responds to medications.

Given that drugs generally target proteins, Van Eyk sees single-cell proteomics as a critical new tool for troubleshooting disease treatments and testing new ones.

Van Eyk’s research appears in the journal Molecular and Cellular Proteomics, titled “Single-Cell Proteomics Reveals Specific Cellular Subtypes in Cardiomyocytes Derived From Human iPSCs and Adult Hearts.”