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Human BioMolecular Atlas Program Presents Reference Cell Maps of Human Organs

NEW YORK — Several research groups have compiled reference cell maps of various human organs, providing insight into how cells arrange and interact in healthy organs compared to diseased ones.

The authors described their findings in nine papers published in various Nature journals and Cell Reports on Wednesday. The research was led by the Human BioMolecular Atlas Program (HuBMAP), a National Institutes of Health-funded consortium which aims to create a framework for the whole human body at a single-cell resolution.

Armed with techniques such as single-cell RNA sequencing, mass spectrometry, 3D imaging with spatial transcriptomics, and AI, the researchers took a zoomed-in view of the cellular architecture. 

For one of the studies in Nature, a team of Stanford University researchers analyzed eight sections of the human intestine from nine people. Of these, seven samples came from individuals of European descent, and two were of African American backgrounds.

Using multiplexed imaging, single-nucleus RNA-seq, the assay for transposase-accessible chromatin with sequencing (ATAC-seq, which measures open chromatin in a single cell), and CODEX (which stains tissue sections with up to 54 antibody probes), the authors saw some unique features of the 9-meter-long human intestine. For instance, they found 25 different cell types, including new secretory cells in the organ's duodenum region.

The authors said the cells in the intestine had specific organizations or neighborhoods. "These vary across the intestine, which probably represents different functions," co-corresponding author Michael Snyder from the Department of Genetics at Stanford School of Medicine said in a press briefing. "There is a hierarchical organization of the cells in a very complex fashion."

The researchers also mapped gene regulatory differences in these cells, suggesting a regulatory differentiation cascade.

Other interesting findings were that the number of CD8+ T cells decreased from the small intestine to the colon, and people with hypertension tended to have a higher percentage of these cells, Snyder added.

"These results describe the complexity of the cell composition, regulation, and organization for this organ and serve as an important reference map for understanding human biology and disease," the authors wrote.

Meanwhile, another study in Nature led by researchers at Washington University School of Medicine in St. Louis focused on unraveling the cell types in the human kidney. The study used single-nucleus assays and spatial imaging technologies for kidney tissue samples of 45 healthy donors and 48 patients with kidney diseases.

Their findings showed 51 cell types in healthy kidney samples, some of which were noted in the kidney for the first time. Additionally, the authors found 28 related cell types with features associated with injury or recovery. They also created comprehensive 2D and 3D maps of kidney cell organization and molecular identity in healthy and diseased kidneys. "We found several altered cell states in many different kidney segments, reflecting the plasticity in cell phenotypes as cells transition through healthy, injury, and recovery states," co-corresponding author Sanjay Jain, professor of medicine at Washington University, said in a press statement.

A third study led by another team of scientists at Stanford analyzed around 500,000 cells and 588 arteries from 66 human maternal–fetal interface samples. The researchers aimed to use spatial maps to understand how the placenta's extravillous trophoblasts (EVTs) invade the uterus and remodel the spiral arteries, transforming them into large, dilated blood vessels. "Mother has to develop tolerance to the fetus, and arteries in the uterus undergo dramatic changes to accommodate the fetus's needs," said co-corresponding author Michael Angelo from the Department of Pathology at Stanford University.

The authors found how the composition of maternal immune cells changed over time during the process of trophoblast invasion. "We could determine the gestational age just by looking at the maternal immune cells," Angelo said.

An accompanying News & Views article by Roser Vento-Tormo and Roser Vilarrasa-Blasi from the Wellcome Sanger Institute noted that the three HuBMAP atlases could advance the understanding of diseases by defining the spatial location of cell states linked to diseases.

As next steps, the research groups want to increase the diversity of the samples and include tissues from people of all ethnicities and geographical regions, the authors said in the press briefing.

Presently, data on 31 organs is publicly available. However, HuBMAP aims to have a single-cell resolution of around 70 human organs. "Ultimately, we might have an atlas of every healthy cell in the human body," said Katy Borner, a researcher at Indiana University, who is a member of HuBMAP.