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First cell atlas of human kidney’s immune system created by Sanger Institute, University of Cambridge and Newcastle University




Scientists have mapped nearly 70,000 individual kidney cells from early life and adults to create the first cell atlas of the human kidney’s immune system.

It reveals how the immune system in the organ develops in the foetus and strengthens after birth and as we mature into adults.

A microscopic section of human kidney cortex. Image: Menna Clatworthy, University of Cambridge (19577003)
A microscopic section of human kidney cortex. Image: Menna Clatworthy, University of Cambridge (19577003)

The work, published in Science, was carried out by researchers at the Wellcome Sanger Institute, University of Cambridge, Newcastle University and their collaborators will aid efforts to understand kidney diseases and transplant rejection.

Prof Menna Clatworthy, co-lead author from the University of Cambridge’s Department of Medicine and the Sanger Institute, said: “The kidney cell atlas allows us to chart where different types of immune cells are located in different zones of the kidney.

“We highlighted a strong defence zone at the base of the kidney, near where urine leaves the kidney via the ureter, which fights against urinary tract infections.

“Understanding how different cell types in a healthy kidney protects us against disease is important for tackling the development of chronic kidney disease and identifying new treatments.”

Our kidneys filter about half a cup of blood every minute, removing waste and excess water, which leaves the body as urine.

When they cannot filter blood properly, they lose function, leading to chronic kidney disease, which affects more than 850 million worldwide.

Commonly caused by diabetes, high blood pressure and recurring infections, this can lead to kidney failure, which is fatal unless a transplant is carried out.

The researchers sequenced the activity of genes in 67,471 individual cells, using single-cell RNA sequencing, to learn what types of immune cells were present. They mapped them over time and within the anatomy of the kidney to understand the development and organisation of the organ’s immune system.

Macrophages - large white blood cells that consume bacteria, viruses, fungi and parasites - were the earliest cells to populate the developing kidney, and these stay in the organ as we grow.

But overall the team found few active immune cells in the developing kidney, which supports the theory that a baby first encounters bacteria during and after birth - a process that activates the immune system.

Dr Sam Behjati, co-lead author from the Wellcome Sanger Institute and University of Cambridge, said: “The kidney cell atlas provides a window to understand what happens in diseases in children, including childhood kidney cancers. The atlas will allow researchers to ask fundamental questions about disease, like why some patients respond to treatment and others do not.”

Dr Sarah Teichmann, co-lead author from the Wellcome Sanger Institute and University of Cambridge, and co-chair of the Human Cell Atlas initiative organising committee, said: “Mapping the human kidney brings us one step closer to producing the Human Cell Atlas – a Google map of the 37 trillion cells in the human body. We will discover new cell types and uncover how our cells change over time, learn how and why we age and what happens when we get a disease. The Human Cell Atlas will be a free online resource, for anyone to use.”

The data is available for researchers to use at kidneycellatlas.org.

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