Human Cell Atlas project transforms understanding of human body

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An ambitious plan to map all 37 trillion cells in the human body is transforming understanding of how our bodies work, scientists report.

The received wisdom said we were built from around 200 types of cell – such as heart muscle or nerve cells.

Instead the Human Cell Atlas project has revealed there are thousands of cell types, with some appearing to be culprits in diseases such as inflammatory bowel disease and cystic fibrosis.

In a flurry of announcements, the formation of the human skeleton and the early immune system have also been mapped out in detail.

The novel insight is akin to moving from the maps of the 15th Century era of Joan of Arc and Richard III to what the phone in your pocket can load.

The old maps of the body had the equivalent of major roads and significant geography but also areas cartographers labelled unknown or “terra incognita”.

“[Now] it looks more like a Google map, you have a high resolution view and then on top of that you have the Street View that explains what’s going on, and then on top of that you can see the dynamic changes during the day when less cars are flowing or more cars are flowing,” said Dr Aviv Regev, one of the founders who now works at now at Genentech.

She added: “This is essential for us to understand and treat disease, cells are the basic unit of life, if things go wrong, they go wrong with our cells.”

Performing a feat of “human cartography” requires cutting-edge biology and computer science.

The project so far has looked at more than 100 million cells – deeply analysing each individual one – from 10,000 people around the world.

The journal Nature has now published a series of 40 scientific discoveries as researchers work towards creating the first draft of the whole human cell atlas.

“This is a major milestone that marks a great leap in understanding of the human body,” said Dr Sarah Teichmann, from the University of Cambridge and one of the founders of the Human Cell Atlas.

Broad Institute A kaleidoscopic image of the cells of the small intestine ranging from bright reds to deep purples. Broad Institute

The human small intestine

The latest discoveries include a map of the gut all the way from the mouth, down the oesphagus, into the stomach and intestines and out the anus.

Researchers looked at the types of cells, where they were located and how they chatted to the other cells around them.

Out of the 1.6 million cells analysed was a new form, called a gut metaplastic cell. It seems to play a role in exacerbating inflammation in the seven million people that live with inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease.

“We were able to uncover a pathogenic cell type that may play a role in some chronic conditions and could be a target for [drug] intervention in the future,” said Dr Rasa Elmentaite, who did the research at the Wellcome Sanger Institute.

There are more than 3,600 scientists across 100 countries collaborating on the Human Cell Atlas, which is one of the most ambitious projects in biology and has been described as the heir to the Human Genome Project to sequence the human genetic code.

The developing human skeleton where cartilage (blue) acts as a ‘scaffold’ before bone (purple) is formed.

Another discovery showed how the human skeleton forms in the womb in the weeks after conception.

First a scaffold of cartilage, like the wobbly bit on the end of your nose, forms. Then bone cells grow over it. This happens everywhere except for the very top of the skull to give the brain space to grow.

Some of the genetic instructions involved in orchestrating this early developmental process are the same ones implicated in osteoarthritis decades later.

“Ultimately, using this atlas could help us better understand the conditions of both the young and ageing skeleton,” said Dr Ken To, from the Wellcome Sanger Institute.

A similar study looked at the thymus – a small organ involved in training the immune system. Researchers showed this process started much earlier than previously thought suggesting the earliest stages of pregnancy could have an impact on immune function for life.

It also gives ideas for engineering new immune-cell-based therapies in the laboratory for fighting diseases such as a cancer.

Another example of the Human Cell Atlas in action came during the Covid pandemic when the detailed maps of the body allowed scientists to anticipate how the virus would move from tissue to tissue and identified the nose, mouth and eyes as key entry points to the body.

Dr Katrina Gold, from the Wellcome Trust medical research funder, said today’s announcements were a “true milestone for the Human Cell Atlas”.

“When complete, it could transform the ways we diagnose, monitor and treat diseases,” she said.

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