DNA is the blueprint which gives our cells instructions, but all of our cells have the same set of instructions, so to understand how cells behave differently we need to look at each one more deeply and explore which of the thousands of genetic instructions are turned off and on at any time.
In recent years, the study of gene expression has focused on sequencing molecules inside the cells called mRNA. However, these are only the copies of the genetic instructions, not the proteins that are built from those instructions. Now, scientists at the Finsen Laboratory and BRIC, DTU and the Helmholtz Munich have used a method called single-cell proteomics analysis which looks at the unique combination of proteins being built in each cell at any given moment in its development.
This analysis bypasses the mRNA intermediates and builds a map of the proteins present in each cell during their differentiation from stem cells into mature blood cells. Looking at each cell makes it possible to identify outliers that would otherwise be lost in the average of the sample.
Bo Porse, of Finsen Lab and BRIC, says: “The process of cell differentiation is immensely complex, and we need to fully understand the nuances of what’s happening inside each cell at each stage of its life to address the cases when the process goes wrong. With this study we’ve shown the feasibility of using this technology to accurately model the exact stages of gene expression, covering both mRNA synthesis and decay, and subsequent protein synthesis and decay throughout cell differentiation”.
“This study is the culmination of many years of intense technology development. Not long ago, the idea of measuring thousands of proteins in single human stem cells from the bone marrow felt like science fiction. We never imagined we'd be able to apply scp-MS to something as complex and dynamic as the human blood system this soon. But here we are, finally able to access layers of biology that are completely invisible to RNA-based methods alone. It's a testament to the power of mass spectrometry, protein-level readouts, and data-driven systems biology to transform our understanding of how cells take fate decisions”, says co-senior author Erwin Schoof, Associate Professor and Head of the Cell Diversity Lab at the Department for Biotechnology and Biomedicine at the Technical University of Denmark.
This work is part of the collaboration between Region H and DTU, formalized under the Technical University Hospital of Greater Copenhagen.
Co-Senior Authors
- Bo Porse, of Finsen Laboratory at Rigshospitalet and the Biotech Research and Innovation Centre (University of Copenhagen)
- Fabian Theis, Director at the Computational Health Center at Helmholtz Munich, and Professor for Mathematical Modeling of Biological Systems at the Technical University of Munich.
- Erwin Schoof, Associate Professor and Head of the Cell Diversity Lab at the Department for Biotechnology and Biomedicine at the Technical University of Denmark.
We gratefully acknowledge the support of the Lundbeck Foundation, the Danish Cancer Society, the Independent Research Fund Denmark, and the Novo Nordisk Foundation, which made this work possible.
Read the full article 'Zooming in reveals a world of detail: breakthrough method unveils the inner workings of our cells' in Science.
This article has been adapted with permission from the news article “Ever wonder how blood cells know how to behave?” published on the BRIC/KU website.
