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A new microfluidic method of studying single-cell epigenetics

Valérie Devillaine
06/13/2019
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Researchers at Institut Curie are combining their expertise with that of a team from the ESPCI and HiFiBiO to identify, cell by cell, the epigenetic signature of cells that are resistant to anticancer treatments. This new breakthrough has earned them a publication in Nature Genetics.
Céline Vallot

Microfluidics is a technique that allows single-cell analysis, i.e. to talk of cells individually, rather than observing the average behavior of a large cell population. Using this method, isolating individualized cells in microdroplets, researchers gradually discovered heterogeneity within the cells that make up a tumor. After revealing the genetic differences between different cells, they are now moving to the next level: observing epigenetic differences, no longer looking at DNA composition, but the way in which it is organized.

This study is more complicated than that of RNA (this DNA derivative enables the study of gene expression). This is why researchers at Institut Curie have collaborated with Andrew Griffiths and his team at the ESPCI, the École supérieure de physique et de chimie industrielle de Paris, and Annabelle Gérard from HiFiBio, a specialist microfluidics company. These microfluidics experts are thus associated with the team of Céline Vallot, data analysis specialist at Institut Curie.

Microfluidics is already a leading technique in molecular biology. Together, these researchers are taking it a step further. Keven Grosselin, a PhD student at ESPCI and HiFiBio, developed the technique that applies to epigenetics: “a three-step technique, different to and more complex than usual microfluidics, which examines gene expression,” comments Céline Vallot. For her part, she contributed her data analysis expertise: “The data collected using this technique is very scattered, there are lots of “gaps”, genes about which we have little information. Data processing thus allows the relevant information to be extracted, thereby answering our biological questions”. Through a collaboration with Elisabetta Marangoni and her preclinical investigation team at Institut Curie, researchers were able to examine the epigenetic map in cases of resistance to chemotherapy and hormone therapy.

This is how they revealed epigenetic subclones, the group of cells among the cells of a tumor that have identical characteristics to each other but are different to the rest in terms of epigenetics. “We have observed heterogeneous epigenetic maps within sensitive tumors”, explains Céline Vallot. This may explain how some tumors are resistant to treatment. Thanks to this collaboration, Institut Curie now has this new microfluidics technique, which could enable us to identify a subpopulation of cells, which may only be 16% of the tumor cells, but which could determine the acquisition of resistance.”

Sources

High-throughput single-cell ChIP-seq identifies heterogeneity of chromatin states in breast cancer