Most comprehensive cell map of the human gut produced by Wellcome Sanger Institute and collaborators

The most comprehensive cell map of the human gut to date has been created, which could help provide insights into conditions such as bowel cancer and inflammatory bowel disease (IBD).

Wellcome Sanger Institute researchers and their collaborators combined spatial and single-cell data from 1.6 million cells to create the atlas, and used it to uncover how a specific gut cell is implicated in a cycle of inflammation in some individuals that can cause pain and distress.

The team used a new tool to harmonise more than 25 single-cell datasets from the human gastrointestinal (GI) tract to create the world’s largest freely-available resource of the human gut, with tissue samples from those without GI issues, gastric and colorectal cancers, celiac disease, ulcerative colitis and Crohn’s disease, as well as those without conditions.

The tool, which could also be applied to other organs, helped them create a picture of what cells were present, where they were located and how they communicated with the environment around them.

The hope is this atlas can help illuminate changes or differences that could be involved in the onset of conditions and lead to new targets for drug development.

This paper is one of a collection of more than 40 Human Cell Atlas publications published in Nature portfolio journals.

Dr Amanda Oliver, first author from the Wellcome Sanger Institute, said: “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.

“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 harmonised and freely available, and we hope that people will continue to build on this, adding in data for scientists worldwide to use.”

The team identified that gut metaplastic cells, which are known to be involved in healing the stomach lining, contained genetic similarities to other GI cells involved in inflammation.

They suggest that inflammation in IBD leads to changes in these metaplastic cells, which contributes to inflammatory responses - knowledge that could be used to find way to treat the condition.

Dr Rasa Elmentaite, co-senior author previously at the Wellcome Sanger Institute and currently at Ensocell Therapeutics, said: “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.

“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.”

Professor Sarah Teichmann, co-senior author and co-founder of the Human Cell Atlas, previously at the Wellcome Sanger Institute and now at the Cambridge Stem Cell Institute at the University of Cambridge, said: “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.

“This harmonised 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.”