Chromatin usage in individual cells reveals developmental trajectories

March 14, 2018

Both cell type and developmental stage can be deduced from measurements of chromatin accessibility in thousands of single cells, researchers at EMBL and the University of Washington show. They used this approach to uncover how cells in developing embryos regulate their identity as they decide what kind of cell to become. Nature publishes the results on March 14.

This new and more systematic approach allows researchers to analyse all the different cell types in an embryo at the same time, and importantly at a single cell resolution. "I expect this approach to save labs around the world lots of time," says Eileen Furlong, who co-led the work at EMBL in Heidelberg with Jay Shendure at the University of Washington School of Medicine in Seattle.

Previously, a researcher would have to first isolate the various cell types, and then investigate the chromatin of each type in separate batches. That lengthy method provided an averaged view across thousands of cells of a given cell type. "Previous studies have used differences in RNA content to identify cell types and their developmental trajectories," says Shendure. "Here, we instead measure the state of chromatin in single cells, which contains the regulatory program that governs how and when RNAs are expressed in each cell."

"For the first time, we have looked upstream at how these expression signatures are regulated and therefore drive single cell trajectories during early development," Furlong adds.

Role of chromatin

Chromatin is the tightly-coiled structure of DNA and proteins which is used to store the genetic information inside the nucleus of a cell. The chromatin in a human cell contains around two metres of DNA, packed into a nucleus less than one hundredth of a millimetre across. Regulatory elements like promoters and enhancers are short stretches of DNA that regulate the levels of gene expression and therefore the production of proteins, which are what ultimately make cell types different from one another. When cells use a particular regulatory element, the chromatin uncoils and its content becomes accessible. That's why Furlong, Shendure and colleagues expected chromatin accessibility to shed light on how a cell follows a specific developmental path, turning into a highly specialised muscle or nerve cell, for example.

Having single-cell information on chromatin accessibility allowed the team to determine a cell's identity and how it is regulated. They performed the experiments on fruit fly embryos, a very important model organism for both developmental biology and disease models, but the approach can be applied to any species. The results identified thousands of previously unknown regulatory elements that are used only in a subset of cells and predicted when and where each element are active during development. The data, made available through a user-friendly browser (see below), reveals a wealth of differences between cell types and provides a powerful resource for future studies.

This work was the result of a collaboration between James Reddington and David Garfield in the Furlong group at EMBL, and Darren Cusanovich in Jay Shendure's group at the University of Washington School of Medicine, Seattle. Looking forward, the research team plans to expand this study, and to integrate other layers of single-cell information on the regulation of cell fate decisions during embryogenesis.
-end-
Source article:

Cusanovich, Reddington, Garfield et al., The cis-regulatory dynamics of embryonic development at single cell resolution. Nature, published online 14 March 2018. DOI: 10.1038/nature25981

Suggested links:*EMBL is Europe's flagship laboratory for the life sciences. We are an intergovernmental organisation established in 1974 and are supported by over 20 member states. EMBL performs fundamental research in molecular biology, studying the story of life. We offer services to the scientific community; train the next generation of scientists and strive to integrate the life sciences across Europe.

We are international, innovative and interdisciplinary. We are more than 1600 people, from over 80 countries, operating across six sites in Grenoble (France), Hamburg (Germany), Heidelberg (Germany), Cambridge (UK), Rome (Italy), and Barcelona (Spain). Our scientists work in independent groups and conduct research and offer services in all areas of molecular biology.

Our research drives the development of new technology and methods in the life sciences. We work to transfer this knowledge for the benefit of society.

UW Medicine is one of the top-rated academic medical systems in the world. With a mission to improve the health of the public, UW Medicine educates the next generation of physicians and scientists, leads one of the world's largest and most comprehensive biomedical research programs, and provides outstanding care to patients from across the globe. UW School of Medicine faculty members are second in the nation in receipt of federal research grants and contracts, with $749.9 million in total revenue (fiscal year 2016) according to the Association of American Medical Colleges. For details, see http://www.uwmedicine.org.

European Molecular Biology Laboratory

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.