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Cell mapping: ‘Atlas’ aims to shed light on kidney diseases

The kidney tissue atlas is made up of single-cell maps of healthy as well as diseased cells.

Nilima Marshall
Wednesday 19 July 2023 16:46 BST
The kidney atlas is part of the US’s wider Human BioMolecular Atlas Programme, which aims to map every cell type in the human body in 3D (Lauren Hurley/PA)
The kidney atlas is part of the US’s wider Human BioMolecular Atlas Programme, which aims to map every cell type in the human body in 3D (Lauren Hurley/PA) (PA Archive)

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Scientists have created the most comprehensive “atlas” of the human kidney with the aim of understanding more about how diseases progress in the organ.

Constructed by US researchers, it is made up of single-cell maps of healthy as well as diseased cells, based on tissue samples from more than 90 patients.

It is intended to serve as a foundation for understanding what happens on a cellular level after acute kidney injury, a condition in which the kidneys suddenly lose their ability to filter waste from blood.

Blue Lake, who conducted the research as a project scientist at the University of California, San Diego, in the US, said: “We want to understand that progression at the single-cell level.

By building an atlas of the different types of cells that make up a healthy kidney, as well as injured and diseased kidneys, we can start to figure out which cell types may be contributing to disease progression

Blue Lake, project scientist

“By building an atlas of the different types of cells that make up a healthy kidney, as well as injured and diseased kidneys, we can start to figure out which cell types may be contributing to disease progression.

“We can get an idea of what changes are happening that cause some injured cell types to repair, and in some cases, transition into a state that can no longer be repaired.”

The kidney atlas is part of the US’s wider Human BioMolecular Atlas Programme (HuBMAP), which aims to map every cell type in the human body in 3D.

Scientists who are part of this consortium have also created detailed maps of the human intestine as well as the human placenta during the first half of pregnancy.

Michael Angelo, assistant professor of pathology at Stanford University in the US, and his colleagues analysed around 500,000 cells and 588 arteries from 66 samples of the maternal-fetal interface – where cells from the mother and the placenta form a “unique co-operation” to support the growing baby.

The team mapped the intricate interaction between cells that originate during early embryonic development and the mother’s immune system.

Arteries that embed in the placenta and deliver blood and nutrients from the mother to the baby change their cellular make-up to ensure both cells from the baby and the mother are incorporated into the placenta.

Prof Angelo said: “This was the first study to comprehensively map how spiral arteries change, from un-remodelled to fully remodelled.”

He said this work may lead to treatments for certain types of infertility, and shed further light on why miscarriages occur, which has been linked to problems with the way that the mother’s immune system adapts.

Prof Angelo said: “It would be ideal if we could identify ahead of time who was at risk and give some sort of preparation for the immune system before pregnancy.”

Meanwhile, with a map of the intestine, the researchers are hoping it will shed light on why diseases of the bowel occur and how to find effective treatments.

In research, we have a habit of studying things that are abnormal without really understanding what normal looks like. That's created a big gap in our knowledge

Professor Michael Angelo, Stanford University

Michael Snyder, professor of genetics at Stanford Medicine, said: “Our maps are intended to be a reference for a healthy intestine, with which we can compare everything from irritable bowel disease to early-stage colon cancer.

“This will be foundational for our understanding of all kinds of digestive diseases.”

Ultimately, the aim of HuBMAP is to create a comprehensive resource for researchers to better understand all human tissue across all organs.

Prof Angelo, who is also the co-chair of the HuBMAP steering committee, said: “In research, we have a habit of studying things that are abnormal without really understanding what normal looks like.

“That’s created a big gap in our knowledge.

“HuBMAP is the only effort that is systematically focusing on the spatial architecture of these tissues.”

The scientists said their research complements the work being done by experts involved in the Human Cell Atlas project, led by the Wellcome Sanger Institute in Cambridgeshire.

Prof Angelo said: “Each consortium has a sphere that they are focusing on, and trying to prioritise, and for us, there is a big emphasis being placed on spatial maps, and really looking at the spatial structure of tissue.”

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