Single cell analysis at the heart of the SIRIC program
Recent microfluidics developments have made the sequencing of single cells possible paving the way for numerous applications, for example, tumor heterogeneity analysis: the ability of cells to adapt and diversify during tumor evolution.
With traditional analysis techniques, heterogeneity that exists even within small cell populations leads to measures based on averages that don't take minor but sometimes key changes into account at a single cell level. Studying these changes within each cell could improve our understanding of cell specificities. Mapping modifications at an RNA and protein level or epigenetic modifications in each cell of interest within a given cell population allows researchers to decode the structure of a population, gene expression relations with different phenotypes and heterogeneous apparition of differentiation.
Focus on each cell to understand resistance
In the frame of the SIRIC program, single cell analysis is particularly important for:
- Characterizing intra-population heterogeneity of cancer associated fibroblasts (CAFs)
- Exploring spatial heterogeneity in neuroblastoma
- Studying non genetic cell plasticity at the origin of resistance in pediatric diseases
- Identifying new opportunities in immunothérapy
SIRIC results obtained using single cell analysis
SIRIC: a pioneer of single cell study
1. Acquisition of early expertise
After the acquisition of a C1 Single Cell Auto-Prep System (Fluidigm, ICGex ANR funding) in 2013, SIRIC2011 funded the acquisition of one of the first 10X Genomic Chromium at the heart of the cancer sequencing platform in 2016. The sequencer, installed at the high throughput platform, significantly increased the scale (from 100 to 10 000 cells per test). This increase was an experimental and analytic challenge which required the installation of pipelines and the development of bioinformatic tools (for example, for quantification, normalization and visualization).
Putting this equipment in place early facilitated talent accquisition which was crucial to develop this expertise.
2. Development of custom techniques
SIRIC2018 pursued the investment in single cell techniques with the creation of the single cell platform in June 2018. This is based on a droplet based microfluidic technique and allows researchers to personalize their analysis. It helps users configure pipelines to capture, mark, sort and characterize the phenotype, efficiently sequence thousands of single cells and provide support to analyse generated "large-scale data" (images, sequences, chromatin cards etc).