Mount Sinai researchers have published the first organ-wide human skin spatial atlas from across the body. It provides an unprecedentedly detailed view of healthy human skin, revealing cellular composition and functional mechanisms of skin from more than a dozen unique sites on the body, including the scalp and sole.
The skin is the largest human organ and plays a critical role in regulating body temperature and protecting the immune system as an external barrier. The skin is also susceptible to chronic disease, yet how the skin’s cellular composition and molecular organization vary spatially across the entire body remains largely undefined.
In this landmark study, published in Nature Genetic s on March 23, 2026, Mount Sinai experts constructed a comprehensive mapping of more than 1 million cells from normal adult human skin to identify 45 unique cell types that vary across composition and arrangement in the body. The researchers said this extensive mapping of critical skin cell function brings scientists one step closer to developing more targeted therapeutics that could potentially treat skin diseases like eczema and psoriasis, and restore function to core components of human skin.
Human skin diseases often occur in specific sites; for example, psoriasis frequently appears on the elbows, knees, and scalp. Cells in each region of the skin organize themselves into biological networks composed of diverse cell types that represent communication hubs, working together to maintain immune surveillance or detect pathogens, damaged cells, or early tumors on the skin to eliminate these threats. These systems, otherwise referred to as “multicellular neighborhoods,” are abnormal or impaired when a patient has a skin disease and requires treatment.
In this study, the Mount Sinai team aimed to identify the key molecular factors of these multicellular neighborhoods. The researchers collectively profiled more than 1.2 million cells across 15 anatomic sites from 22 donors to create a skin spatial atlas, a high-resolution map of the location of every individual cell across different layers in healthy human skin across the body. The researchers defined site-specific cell type composition and their organization into 10 recurrent multicellular neighborhoods that vary in their abundance across the body.
One particular neighborhood was composed of immune cells such as dendritic cells and T cells, which work together to train the immune system to attack specific threats, and was located around the skin’s blood vessels. This “perivascular neighborhood” also contained key non-immune cell types, such as a specialized subset of connective tissue cells known as fibroblasts, that are critical for organizing the immune cell positions. The team noted that this perivascular neighborhood is reminiscent of specialized lymphoid tissues in other organs—like tonsils, which are trained to immunologically monitor the oral cavity—and could be considered the skin-associated lymphoid tissue. Within the perivascular neighborhood, the researchers identified the central role of tumor necrosis factor, a chemical messenger known to induce inflammation but which in the context of healthy skin maintains the specialized fibroblasts, highlighting essential communication between structural cells and immune cells.
In a comparison of molecular changes throughout various sites across the body and how neighborhoods are altered by diseases, the researchers noted tissue and organ impairment in the perivascular neighborhood, suggesting cellular alterations when there is disease activity, and thus a potential therapeutic target. The researchers concluded that multicellular neighborhoods underlie the skin’s molecular and structural organization, coordinate cell to cell interactions, guide function, and exhibit structural disruption when a disease is present.
One of the key technological breakthroughs enabling this study is a new method called spatial transcriptomics, which allows high-throughput profiling of hundreds to thousands of genes that are pinpointed to their exact locations within individual cells. By using spatial transcriptomics to profile human skin, the researchers achieved an unprecedented view of the skin from a bird’s-eye level down to smallest genetic detail, comparable to smartphone map apps that allow one to zoom in from a country down to a city block.
“We reasoned that we need to understand what healthy skin looks like in order to fully understand human skin diseases,” said corresponding author Andrew L. Ji, MD, Assistant Professor of Dermatology and a leading researcher in the Black Family Stem Cell Institute, and Kimberly and Eric J. Waldman Melanoma and Skin Cancer Center. “By building this ‘Google Maps’ of skin across the entire body, we found higher-order organization involving these multicellular neighborhoods, wherein diverse cells prefer to be located next to one another. These cell types communicate with each other to maintain healthy function, such as establishing a barrier to the outside world. These neighborhoods can be thought of as the key building blocks of human skin, and we provide the blueprint for how they are constructed and how many comprise each body site. We envision that this atlas will serve as a global foundation, inviting researchers worldwide to layer on new types of data to reveal the full complexities of human skin.”
The discovery of unique cell types and spatial organization in human skin by the Mount Sinai team lays the groundwork for future studies and development of new treatment options for skin diseases, such as tissue engineering and stem-cell therapies, possibly restoring core components of healthy human skin.
New York University and Karolinska Institute in Sweden contributed to the research. The study was supported by funding from the National Institutes of Health (K08CA263187, T32AR082315), and the Damon Runyon Cancer Research Foundation Clinical Investigator Award (121-23).
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Nature Genetics
Single-cell spatial transcriptomic analysis of human skin anatomy
23-Mar-2026