Map of 1.6 million gut cells will reveal new ways to treat disease

A team of scientists led by the Wellcome Sanger Institute has developed the most detailed cellular map of the human gut to date, combining data from 1.6 million cells. 

This atlas provides crucial insights into conditions like bowel cancer and inflammatory bowel disease (IBD) by highlighting cellular changes and interactions within the gastrointestinal (GI) tract.

Published in the journal Nature, the study combined over 25 single-cell datasets to create a unified and freely available resource for researchers worldwide. 

The atlas includes samples from both healthy individuals and those with gut-related diseases, offering a valuable tool for understanding and potentially treating these conditions.

The GI tract and its illnesses

The GI tract comprises organs responsible for digestion and nutrient absorption, including the stomach, intestines, and rectum. It also acts as a barrier against pathogens. Disorders affecting this system, such as IBD and bowel cancer, significantly impact millions of lives globally.

For instance, over seven million people worldwide suffer from IBD, which includes conditions like ulcerative colitis and Crohn’s disease. Symptoms such as abdominal pain, diarrhea, and extreme fatigue often disrupt daily life. 

Meanwhile, bowel cancer, one of the most common cancers globally, affects nearly two million people each year and is the fourth most prevalent cancer in the UK.

A unified picture of gut cells

Despite extensive research, fragmented data from multiple studies with varying processes and labeling systems have complicated efforts to understand the cellular structure of the gut. 

To address this, the Wellcome Sanger Institute team developed a tool to harmonize these datasets, enabling researchers to see a unified picture of gut cells, their locations, and their interactions.

A new resource for gut health research

The researchers merged 25 datasets to create an atlas containing spatial and single-cell data from 1.6 million cells. 

This unified resource includes tissue samples from individuals with conditions like gastric and colorectal cancers, celiac disease, and IBD, as well as from healthy individuals.

The atlas allows researchers to identify which cells are present in the gut, their precise locations, and how they communicate with their environment. 

By integrating this data, the team has created a dynamic resource that can be updated with future studies, enhancing collaboration among scientists worldwide.

“Spatial and single-cell data provide unique information about how gut cells interact, that can be used to continue piecing together an in-depth understanding of how the human body works,” said lead author Amanda Oliver, a scientist at the Wellcome Sanger Institute. 

“Combining existing single-cell datasets allows us to create a more complete picture of the human gut and ensures that researchers can work together to continue to benefit human health.” 

“Our Gut Cell Atlas is also harmonized and freely available, and we hope that people will continue to build on this, adding in data for scientists worldwide to use.”

Insights into gut inflammation

One of the study’s significant findings involves gut metaplastic cells. Previously known for their role in healing the stomach lining, these cells were found to share genetic similarities with inflammatory cells in the gut. 

Researchers suggest that in conditions like IBD, inflammation transforms these metaplastic cells, perpetuating a cycle of inflammation that contributes to pain and distress.

Study co-senior author Rasa Elmentaite is a scientist at Ensocell Therapeutics who previously worked at the Wellcome Sanger Institute.

“As the integrated atlas contains such a large amount of data, from people with and without gut conditions, we were able to uncover a pathogenic cell type that may play a role in some chronic conditions and could be a target for intervention in the future,” said Elmentaite. 

“This demonstrates the power of using integrated single-cell atlases in research, and I am confident that applying this approach to other tissues and organs will drive new therapeutic discoveries for a range of conditions.” 

Understanding this cycle of inflammation could pave the way for innovative treatments for IBD and similar chronic conditions.

Human Cell Atlas initiative

This research is part of the Human Cell Atlas (HCA) initiative, which aims to map every cell type in the human body to better understand human health and disease. 

The Gut Cell Atlas is among more than 40 studies recently published in Nature journals, representing a significant leap in cellular biology and the development of new analytical tools.

Professor Sarah Teichmann, co-senior author and co-founder of the HCA, highlighted the collaborative nature of the project. 

“A detailed understanding of cells through the Human Cell Atlas will help explain many aspects of human health and disease and possibly illuminate new avenues for treatment,” said Teichmann. 

“This harmonized Gut Cell Atlas shows what can be achieved through open collaboration with scientists worldwide, and has led to an accessible combined resource that can be used by everyone to find new ways to understand and treat disease.”

A tool for global collaboration

The Gut Cell Atlas not only advances gut research but also provides a framework for studying other organs. 

Its harmonized data and innovative analytical tools could drive breakthroughs in understanding various conditions and developing new therapies. 

With the resource freely accessible, it stands as a testament to the power of open collaboration in science.

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