What causes some individuals who experience a sudden decline in kidney function to develop kidney disease while others recover? A new study led by bioengineers at the University of California San Diego can provide detailed insight—at the level of individual cells—into the underlying factors that contribute to these different outcomes.
Researchers have constructed the largest single-cell atlas of the human kidney to date mapping healthy and diseased cell states in more than 90 patients. The atlas is intended to serve as a foundation to better understand the progression of kidney disease after acute kidney injury, a condition in which the kidneys suddenly lose their ability to filter waste from the blood.
“We want to understand that development at the single-cell level,” said study co-first author Blue Lake, who led this research as a project scientist in the Department of Bioengineering at UC San Diego. “By creating an atlas of the different types of cells that make up a healthy kidney, as well as injured and diseased kidneys, we can begin to figure out which types of cells might be contribute to the development of the disease. We can get an idea of what the changes are. The events that cause some injured cell types to heal, and in some cases, transition to a state that is not to be fixed.”
The work, titled “An atlas of healthy and injured cell states and niches in the human kidney” and published on July 19 in the journal NATUREThe lab was jointly led by former UC San Diego bioengineering professor Kun Zhang, who is now at the San Diego Institute of Science, Altos Labs, and researchers at Washington University, Indiana University, and the University of Michigan.
To build their atlas, the researchers analyzed more than 400,000 cells and nuclei from multiple kidney samples from individuals with healthy kidneys, acute kidney injury, and chronic kidney disease.
Single-cell and single-nucleus sequencing technologies are used to generate RNA expression and gene expression profiles of cells. These profiles enabled the researchers to identify 51 different populations of cell types. Using spatial imaging technologies, researchers were able to map where different cell types are arranged in the kidney.
“This is the most comprehensive atlas to date of human kidney cell types,” Lake said.
The researchers also discovered that 28 of these cell types are altered in acute kidney injury.
What usually happens when kidney cells are injured is that they enter a state of repair where they make new copies of themselves, as well as release signals that recruit immune cells and fibroblasts. , to heal the injured area. Afterwards, they return to their normal cellular state.
But with altered cell types, the return to normal state does not occur, the researchers found. However, they are stuck in a state of repair. As a result, they continue to recruit more immune cells and fibroblasts. This induces inflammation and fibrosis, which also leads to disease progression and irreversible decline in kidney functions.
“These repair states are often important for recovery but can be maladaptive,” Lake said. “If they persist or are constantly stimulated, that causes the kidney to continue in a diseased state.”
The researchers found that these altered cell types, which have a so-called “maladaptive repair state,” reside in both parts of the nephrons, which are the primary filtering units of the kidney. The first area is called the proximal tubule, known from previous studies in mice. This new study reveals that the second part of the nephron, called the thick ascending limb, is also located in these altered cell types.
“We were surprised to see that this maladaptive state of repair appeared in human cells elsewhere,” Lake said. “We have now identified another area of the kidney that may be involved in the development of the disease.
Researchers are building the next version of their kidney atlas. Their goal is to include data from a more diverse population of patients.
An atlas of healthy and injured cell states and niches in the human kidney, NATURE (2023). DOI: 10.1038/s41586-023-05769-3
Provided by the University of California – San Diego
Citation: Single-cell atlas of human kidney provides new resources to study kidney disease (2023, July 19) retrieved on July 19, 2023 from https://phys.org/news/2023- 07-single-cell-atlas-human-kidney -resources.html
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