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Updated: Sep 15, 2025

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Lymphocyte Isolation from Human Skin for Phenotypic Analysis and Ex Vivo Cell Culture
Published on: April 8, 2016
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Lineage memory shapes viral resistance barriers in human skin
Laura C Van Eyndhoven1, Grant Kinsler1, Jingchao Zhang2
1Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Biorxiv : the Preprint Server for Biology
|July 16, 2025
Summary
Cellular lineage, not just chance, determines viral resistance in human skin. This inherited cell memory blocks viral spread, offering new insights into infection dynamics and containment.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Individual cells show varied susceptibility to viral infections.
- It is unclear if this variability stems from inherited cell memory or random chance.
Purpose of the Study:
- To investigate whether viral resistance is encoded in cellular lineages.
- To understand the mechanisms behind heritable antiviral resistance in human skin cells.
Main Methods:
- Utilized multi-color lineage tracing in a human primary organotypic skin model.
- Performed ATAC and proteomics profiling on resistant and susceptible cell clones.
- Investigated the role of transcription factor AP-1 in viral resistance.
Main Results:
- Viral resistance is encoded within specific cellular lineages, creating boundaries that impede viral spread.
- Viral susceptibility demonstrated strong heritability across cell generations.
- Distinct epigenomic and proteomic states were identified in resistant versus susceptible clones, with AP-1 identified as a key regulator.
- PMA-induced AP-1 activity conferred viral resistance, suggesting a causative role in memory.
Conclusions:
- Antiviral resistance in human skin cells is encoded in cellular lineages and maintained through cell division.
- Cellular memory plays a significant role in shaping infection dynamics and viral containment within tissues.
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