2023-07-19 17:00:17
The trillions of cells of the human being must be organized in 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 us to map our bodies with a single cell resolution
In three articles published this week in Nature Reference cell maps of the human intestine, kidney and maternal-fetal interface (where the placenta and maternal cells coexist).
Scientists have used the most advanced methods to image single cells and characterize the structures and organs of the body.
The papers are part of a larger package of articles from the Human BioMolecular Atlas Program (HuBMAP) published in the magazines of the group 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 human biology and disease.
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 USA. 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.
Gut neighborhoods
The team of Michael Snydera geneticist at Stanford University (USA), observed the human intestinea 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 the different regions.
“We discovered that cells organize themselves into different arrangements called neighborhoods that help define its function”, explains Snyder to SINC. Like human neighborhoods, which have common elements such as streets, restaurants, and houses, these groups of cells are made up of various quantities and types with specific functions. “So cells aren’t just cells, it’s important who they’re with.”
Cellular-scale image of the small intestine. / John Hickey/Garry Nolan Lab.
The researchers also discovered 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 cancer
Michael Snyder (Stanford University)
“What is special is that we are generating healthy organ data 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”, stresses the geneticist.
Among other findings, Snyder also mentions that “CD8 T cells, which are involved in defense against pathogens, decrease from the small to the large intestine, and are less present in people with hypertension”. In addition, “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 diseased human kidneys. Damage to these organs can trigger cell changes that ultimately affect kidney function.
The researchers built 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 for better understanding the progression of kidney disease after acute injury, which causes the kidneys to suddenly lose their cability to filter waste from the blood.
This map can be very useful to treat diabetes, hypertension, acute injuries, kidney failure or chronic kidney disease.
Sanjay Jain (Washington Medical School)
This atlas can be especially useful for treating “diabetes, hypertension, acute injuries, kidney failure or chronic kidney disease”, stresses SINC Sanjay Jainan 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 the success or failure of repair pathways.
“Integration and analysis of data sets from multiple sources and technologies has been one of the main challenges,” 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. The researchers are preparing the next version of the atlas with the intention of including data from a more diverse patient population.
transforming placenta
Early in pregnancy, cells on the fetal side of the developing placenta invade the uterine endometrium and they work with the mother’s immune system to remodel the arteries. “When I read it for the first time, I thought: this is very strange,” confesses the pathologist Michael Angelofrom Stanford University.
The researcher and his colleagues constructed a map of the human placenta during the first half of pregnancy. analyzed about 500,000 cells and 588 arteries from 66 samples human fetal-maternal interface (where maternal and placental cells cooperate to hold the fetus). Specifically, they looked at the tissue in which maternal arteries are remodeled to supply blood to the fetus.
The growth of the placenta on the wall of the uterus can cause problems if it is too big or small.
Studying how the human placenta forms is difficult because it is especially invasive and grows deeper in the uterus than in other mammals. An excessive or insufficient growth of the placenta in the uterine wall can lead to health problems. Knowing the details of ideal development could help you understand what is wrong with pregnancy complications.
The maps cover different stages 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.
Cellular scale image of a human placenta. / Santhosh Sivajothi/Jackson Lab.
The team’s current goal is to determine how they can apply these findings to advance patient care. 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 get through the first trimester”, he explains.
Cellular function, an indicator of health
Healthy tissue atlases play a fundamental role in biomedical research by serving as reference comparable with diseased samples. These maps help to understand what is wrong in the initial stages of the disease. This knowledge can provide key ideas for developing treatments in the early stages of ailments.
Single-cell resolution allows understanding of diseases in their earliest stages
“The three HuBMAP atlases have the potential to advance our understanding of disease by defining the spatial localization of disease-related cellular states,” they write. Roser Vento-Tormo y Vilarrasa-Blasi rose garden In an opinion piece on Nature.
Scientists anticipate the generation of new maps in other fabricsbut note that additional testing still needs to be done on more samples to “establish robust associations between cellular organization and function in health and disease.”
References:
Snyder, M et al. “Organization of the human intestine at single-cell resolution” Nature (2023)
Jain, S. et al. “An atlas of healthy and injured cell states and niches in the human kidney” Nature (2023)
Angelo, M. et al. “A spatially resolved timeline of the human maternal–fetal interface” Nature (2023)
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