They create three atlases of the kidney, intestine and placenta at single-cell resolution

Hundreds of scientists from the Human BioMolecular Atlas Program have mapped the functions and interactions of cells in different tissues and organs. The information makes up a important resource to understand what goes wrong in the early stages of diseases, such as colon cancer, kidney failure or infertility, and thus develop new treatments.

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The trillions of human cells must be organized into precise patterns so that tissues and organs function properly. An international team of more than 400 researchers have come together to create a framework that allows our body to be mapped with a single cell resolution.

In three articles published this week in Nature reference cellular maps of the human intestine, kidney and maternal-fetal interface (where the placenta and maternal cells coexist).

The works are part of a broader package of articles from the Human BioMolecular Atlas Program (HuBMAP) published in the group's journals Nature. The goal is to discover new information about how cell types are organized and how they interact in different human tissues and organs, providing a resource for the study of biology and human diseases.

Besides. They make up the first collection of maps generated by scientists from institutions supported by HuBMAP, which is managed by the National Institutes of Health (NIH) in the US. The authors have used the most advanced methods to obtain images of a single cell and characterize the structures and organs of the human body.

Neighborhoods of the intestine

- Michael Snyder, a geneticist at Stanford University (USA), observed the human intestine, a complex organ with many different structures and functions, from digestion to immune system support. Eight sections from nine individuals were analyzed, revealing drastic variations in the cellular composition of different regions.

“We discovered that cells organize themselves into different arrangements called neighborhoods that help define its function,” Snyder explains to SINC. Like human neighborhoods, which have common elements such as streets, restaurants, and houses, these cell groups are made up of various quantities and types with specific functions. “So, cells are not just cells, but it is important who they are with.”

The researchers also found that some neighborhoods are specifically primed to mediate immune responses. The findings reveal the complex and varied cellular composition that contributes to the functioning of this organ.

«We are generating data from healthy organs. This is crucial to understanding all ailments. In the case of the intestine, the main ones would be inflammatory disease and colon cancerMichael Snyder” (Stanford University).

“What is special is that we are generating data from healthy organs and this is crucial to understanding all ailments. In the case of the intestine, the main ones would be inflammatory bowel disease and colon cancer,” emphasizes the geneticist.

Among other findings, Snyder also mentions that “CD8 T cells, which participate in defense against pathogens, decrease from the small to the large intestine, and are less present in people with hypertension”. Furthermore, “M1 macrophages, responsible for protecting the intestine, decrease in people with a high body mass index.”

The largest single-cell atlas of the human kidney

A group led by bioengineers from the University of San Diego (California, USA) examined the cells of 45 healthy and 48 sick human kidneys. Damage to these organs can trigger changes in cells that ultimately affect kidney function.

The researchers constructed the largest single-cell atlas of the human kidney to date, mapping the states of healthy and diseased cells in more than 90 patients. The map is intended to serve as a basis to better understand the progression of kidney disease after an acute injury, which causes the kidneys to suddenly lose their function.ability to filter waste from the blood.

 "This map can be very useful in treating diabetes, hypertension, acute injuries, kidney failure or chronic kidney diseaseSanjay Jain" (Washington School of Medicine).

This atlas can be especially useful to treat “diabetes, hypertension, acute injuries, kidney failure or chronic kidney disease,” highlights SINC. Sanjay Jain, an ephrologist at the Washington School of Medicine (USA) and leader of this study.

According to the author, this work also identified the states and neighborhoods of immune, stromal, and epithelial cells of the kidney that are altered by acute or chronic injury, including conditions related to successful or failed repair pathways.

“Integrating and analyzing data sets from multiple sources and technologies has been one of the main difficulties,” explains Jain. To build their map, the team analyzed more than 400.000 cells and nuclei from a wide range of kidney samples from individuals with healthy kidneys, acute injuries, and chronic kidney disease. Researchers are preparing the next version of the atlas with the intention of including data from a more diverse patient population.

Placenta in transformation

Early in pregnancy, cells on the fetal side of the developing placenta invade the uterine endometrium and they collaborate with the mother's immune system to remodel the arteries. “When I first read it, I thought: this is very strange,” confesses the pathologist Michael Angelo, from Stanford University.

The researcher and his colleagues built a map of the human placenta during the first half of pregnancy. They analyzed about 500.000 cells and 588 arteries from 66 samples of the human maternal-fetal interface (where maternal and placental cells cooperate to hold the fetus). Specifically, they analyzed the tissue in which maternal arteries remodel to supply blood to the fetus.

Studying how the human placenta is formed is complicated because it is especially invasive and grows deeper in the uterus than in other mammals. Excessive or insufficient growth of the placenta in the uterine wall can lead to health problems. Knowing the details of ideal development could help understand what goes wrong in pregnancy complications.

«Placenta growth on the wall of the uterus can cause problems if it is too large or small«

The maps cover different phases of development (from six to 20 weeks of gestation) and identify interactions between placental and immune cells. This latest discovery sheds light on how this second cell type supports the coexistence of different maternal and fetal cells.

The team's current goal is to determine how they can apply these findings to advance health care for the pregnancy, transplants and even cancer. According to Angelo, this work could help explain certain types of infertility and develop a treatment.

Previous research suggests that some miscarriages occur because the immune system fails to accommodate sufficient development of the placenta to maintain the pregnancy. “Get the maternal-fetal tolerance around the second or third month of pregnancy is essential to overcome the first trimester,” he explains.

Cellular function, an indication of health

Healthy tissue atlases play a fundamental role in biomedical research by serving as comparable reference with diseased samples. These maps help to understand what goes wrong in the initial stages of the disease. This knowledge can provide key ideas to develop treatments in the early stages of ailments.

«Single-cell resolution allows us to understand diseases in their earliest stages«

"The three HuBMAP atlases have the potential to advance our understanding of diseases by defining the spatial localization of cellular states related to them," they write. Roser Vento-Tormo y Roser Vilarrasa-Blasi in an opinion article in Nature.

Scientists predict the generation of new maps in other tissues, but they note that additional testing still needs to be done on more samples to “establish strong associations between cell organization and function in health and disease.”

Source: Sinc Agency