Discovery allows scientists to index thousands of cells simultaneously, a 40-fold increase from the current method

April 9, 2018, Oregon Health & Science University
Credit: CC0 Public Domain

Of the 37 trillion cells in the typical human body, the ability to distinguish one type of cell from another isn't as straightforward as you may think.

OHSU scientists have for the first time developed a method to quickly and efficiently recognize the subtypes of within the body. Led by researchers in the lab of Andrew Adey, Ph.D., the discovery will improve understanding of disease at the molecular level. This ultimately could enable the development of precise treatments of conditions such as cancer, disorders that destroy neurons in the brain, and diseases that affect the heart and blood vessels.

The findings will be published April 9 in the journal Nature Biotechnology.

The new technology provides a method to scale up a previously known method for profiling cell types distinguished by the pattern of studding their DNA.

"It will be incredibly valuable in any environment where there is cell type heterogeneity [diversity]," said Adey, senior author, assistant professor of molecular and medical genetics in the OHSU School of Medicine and a member of the Knight Cardiovascular Institute. "The major areas of interest will be cancer and neuroscience, but we are also applying it to cardiovascular disease."

All cells carry the same genome, the complete set of genes encoded within the cell. The pattern of which genes are expressed in a given cell is what distinguishes a neuron from, say, a liver cell. Even then, it turns out that there are distinctions between similar cells. In 2017, scientists demonstrated a way of discerning subtypes of neurons by measuring the chemical markers between them—the pattern of methyl groups connected to its DNA, known as its methylome.

The new research by Adey and co-authors develops a method for profiling the methylome of large numbers of at one time by adding unique DNA sequence combinations, or indexes, to each cell that are read out by a sequencing instrument. The scientists used the new indexing method on several human cell lines and from a mouse brain to reveal the methylome of 3,282 single cells. That's roughly a 40-fold increase in throughput from the existing of single-cell sequencing.

"We can profile thousands of cells simultaneously," Adey said. "This technology reduces the cost to prepare single-cell DNA methylation libraries to less than 50 cents per cell from $20 to $50 per cell."

Explore further: New genome-mapping technique opens new avenues for precision medicine

More information: Highly scalable generation of DNA methylation profiles in single cells, Nature Biotechnology (2018). nature.com/articles/doi:10.1038/nbt.4112

Related Stories

Democratizing single-cell analysis

March 15, 2018

Scientists at the Allen Institute and the University of Washington have developed a new low-cost technique for profiling gene expression in hundreds of thousands of cells. Split Pool Ligation-based Transcriptome sequencing ...

New kinds of brain cells revealed

August 10, 2017

Under a microscope, it can be hard to tell the difference between any two neurons, the brain cells that store and process information. So scientists have turned to molecular methods to try to identify groups of neurons with ...

Single-nucleus RNA sequencing, droplet by droplet

August 28, 2017

Last year Broad researchers described a single-nucleus RNA sequencing method called sNuc-Seq. This system enabled researchers to study the gene expression profiles of difficult-to-isolate cell types as well as cells from ...

Researchers measure gene activity in single cells

March 16, 2018

For biologists, a single cell is a world of its own: It can form a harmonious part of a tissue, or go rogue and take on a diseased state, like cancer. But biologists have long struggled to identify and track the many different ...

Computer program detects differences between human cells

October 10, 2017

"How many different cell types are there in a human body? And how do these differences develop? Nobody really knows," says Professor Stein Aerts from KU Leuven (University of Leuven) and VIB, Belgium. But thanks to a new ...

Recommended for you

Researchers find positive visual contagion in Barbary macaques

December 12, 2018

A pair of researchers at the University of Roehampton has found that captive Barbary macaques are capable of engaging in positive visual contagion—a behavior normally only seen in humans. In their paper published in Proceedings ...

Hot possums risk losing their homes

December 12, 2018

As our world is warming under climate change, heat waves are becoming more frequent and intense, yet the vulnerability of our wildlife to such events is poorly understood. New research from Australia's Wet Tropics indicates ...

The real history of quantum biology

December 12, 2018

Quantum biology, a young and increasingly popular science genre, isn't as new as many believe, with a complicated and somewhat dark history, explain the founders of the world's first quantum biology doctoral training centre.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.