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Developmental cell programs are co-opted in inflammatory skin disease.

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Researchers profiled over 500,000 single cells from human skin to understand immune cell development and disease. They found prenatal immune cell programs reemerge in inflammatory skin conditions like atopic dermatitis and psoriasis.

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Area of Science:

  • Immunology
  • Developmental Biology
  • Dermatology

Background:

  • The skin provides essential protection via a complex cellular network formed during embryonic development.
  • Understanding the dynamic interplay of skin cells during development and disease is crucial for treating inflammatory skin conditions.

Purpose of the Study:

  • To compare cell states across human skin development, homeostasis, and disease (atopic dermatitis and psoriasis).
  • To identify and validate the reemergence of prenatal cellular programs in adult inflammatory skin diseases.

Main Methods:

  • Single-cell RNA sequencing (transcriptome profiling) of over 500,000 cells.
  • Analysis of developing human fetal skin, healthy adult skin, and diseased adult skin.
  • In situ validation of identified cellular programs.

Main Results:

  • An enrichment of innate immune cells was observed in skin during the first trimester of development.
  • Clonal expansion of disease-associated lymphocytes was identified in atopic dermatitis and psoriasis.
  • Prenatal vascular endothelial cell and macrophage programs were found to reemerge in lesional skin of atopic dermatitis and psoriasis.

Conclusions:

  • Cutaneous immunity is highly dynamic, with developmental programs influencing disease states.
  • The reemergence of prenatal cellular programs in inflammatory skin diseases presents potential therapeutic targets.
  • This study provides a comprehensive single-cell atlas of human skin across development and disease.