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Multicellular ecosystems: Linking cellular diversity to tissue function and disease.

Tissue function emerges from coordinated interactions among diverse cell populations, whereas disruption of these interactions can lead to dysfunction. Recent advances in single-cell and spatial genomics have not only cataloged cellular diversity but also revealed how tissues are organized as dynamic multicellular ecosystems. Moving beyond descriptive cell atlases toward functional, system-level representations represents a major frontier in tissue biology. In this review, we outline conceptual and methodological frameworks for dissecting multicellular coordination, highlight recurrent multicellular ecosystems across physiological and pathological contexts, and explore translational opportunities such as patient stratification, therapeutic reprogramming, and regenerative strategies. Viewing tissues through an ecosystem lens provides a unifying framework that links cellular diversity to emergent tissue function and informs strategies for disease intervention.

Humans

A single-cell spatial transcriptomic census of human skin anatomy.

The skin is the largest human organ and a site of significant disease burden, yet its cellular and molecular organization across the body are largely undefined. Here, we construct a spatially-resolved single-cell atlas of 1.2 million cells from normal adult human skin to localize 45 cell types across 15 anatomic sites. We define principles of organ-wide cell composition, including axes of cell diversity and specialization, and distinguish site-enriched cell types. Each body site is comprised of 10 multicellular neighborhoods that define cell-cell communication. Notably, we identify a perivascular neighborhood enriched for immune-stromal crosstalk with features resembling a homeostatic immune niche similar to skin-associated lymphoid tissue. Finally, mapping these neighborhoods onto skin disease reveals pathogenic neighborhood disruptions, including pan-disease immune alterations in the perivascular neighborhood. We present a framework charting the skin's multiscale spatial organization across a molecular to macroanatomic scale. This work advances our understanding of organ-wide skin cellular organization and communication, and its architectural disruption in disease.

Journal Article