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New, rapid and robust method for single cell profiling

Hope for better understanding of the inner works of cancer and other serious diseases.

By Birgitte Svennevig, , 12/17/2018

Many of the cell types in our bodies work in obscure ways, that science does not yet fully understand. That also goes for immune cells, which are vital for protecting us against serious diseases.

In order to overcome this obstacle, researchers put a lot of effort into finding new ways to study the inner works of individual cells.

- The challenge is not only to isolate an individual cell from a tissue sample. We also need to find a way to determine the function of the individual cell, says Kedar Nath Natarajan, Assistant Professor and Principal Investigator at Department of Biochemistry and Molecular Biology, University of Southern Denmark.

Published in Nature Communications

In a new study, led by Kedar Nath Natarajan and Xi Chen from Wellcome Sanger Institute, a research team has developed a new method for microscopically profiling tiny single cells within organs and tissues. The work is published in Nature Communications.

The new method allowed them to analyse more than 3000 cells from the spleen, which is a hotspot for all kinds of immune cells; cells which fight infections, but also render daily immunity and response.

New methods are constantly being developed to microscopically profile tiny single cells within organs and tissues. The principle is to study the basic blueprint of an organism i.e. DNA and how it is packaged within a single cell. This packaging is referred to as chromatin and signals which genes within the blueprint are switched on and off, thus determining whether it becomes a blood cell, a skin cell, an immune cell, a cancer cell or another type of cell.

- Our new method profiles chromatin within single cells and offers a robust, scalable and cheaper alternative to current state-of-art methods, which require expensive infrastructure, specialized reagents and equipments, said Kedar Nath Natarajan.

Together with first author Xi Chen from Wellcome Sanger Institute, he has lead the development of the new methods and profile different kinds of cells including immune cells, stem cells etc. The other contributors from Wellcome Sanger Institute are Ricardo J Miragaia and this work was performed in the lab of the corresponding author Sarah A Teichmann.

The paper’s abstract

The assay for transposase-accessible chromatin using sequencing (ATAC-seq) is widely used to identify regulatory regions throughout the genome. However, very few studies have been performed at the single cell level (scATAC-seq) due to technical challenges. Here we developed a simple and robust plate-based scATACseq method, combining upfront bulk Tn5 tagging with single-nuclei sorting. We demonstrated that our method worked robustly across various systems, including fresh and cryopreserved cells from primary tissues. By profiling over 3,000 splenocytes, we identify distinct immune cell types and reveal cell type-specific regulatory regions and related transcription factors.

Paper ref: A rapid and robust method for single cell chromatin accessibility profiling. Xi Chen1, Ricardo J Miragaia1,4, Kedar Nath Natarajan1,5, Sarah A Teichmann1,2,3,*
1Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom 2EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom 3Theory of Condensed Matter, Cavendish Laboratory, 19 JJ Thomson Ave, Cambridge, CB3 0HE, UK 4Present address: MedImmune, Sir Aaron Klug Building, Granta Park, Cambridge, CB21 6GH, United Kingdom 5Present address: Functional Biology and Metabolism Unit, Biochemistry and Molecular Biology, SDU, 5230 Odense, Denmark.


Kedar Natarajan is a Principle Investigator at Dept. of Biochemistry and Molecular Biology.

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