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Increased presence and differential molecular imprinting of transit amplifying cells in psoriasis

Abstract

Psoriasis is a very common chronic inflammatory skin disease characterized by epidermal thickening and scaling resulting from keratinocyte hyperproliferation and impaired differentiation. Pathomechanistic studies in psoriasis are often limited by using whole skin tissue biopsies, neglecting their stratification and cellular diversity. This study aimed at characterizing epidermal alterations in psoriasis at the level of keratinocyte populations. Epidermal cell populations were purified from skin biopsies of psoriasis patients and healthy donors using a novel cell type-specific approach. Molecular characterization of the transit-amplifying cells (TAC), the key players of epidermal renewal, was performed using immunocytofluorescence-technique and integrated multiscale-omics analyses. Already TAC from non-lesional psoriatic skin showed altered methylation and differential expression in 1.7% and 1.0% of all protein-coding genes, respectively. In psoriatic lesions, TAC were strongly expanded showing further increased differentially methylated (10-fold) and expressed (22-fold) genes numbers. Importantly, 17.2% of differentially expressed genes were associated with respective gene methylations. Compared with non-lesional TAC, pathway analyses revealed metabolic alterations as one feature predominantly changed in TAC derived from active psoriatic lesions. Overall, our study showed stage-specific molecular alterations, allows new insights into the pathogenesis, and implies the involvement of epigenetic mechanisms in lesion development in psoriasis.

Key messages

  • Transit amplifying cell (TAC) numbers are highly increased in psoriatic lesions

  • Psoriatic TAC show profound molecular alterations & stage-specific identity

  • TAC from unaffected areas already show first signs of molecular alterations

  • Lesional TAC show a preference in metabolic-related alterations

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Acknowledgments

We would like to thank Jenny Kirsch and Toralf Kaiser from the Flow Cytometry Core Facility of the German Rheumatism Research Center (DRFZ, Berlin, Germany) for their kind support in performing cell sorting experiments.

Funding information

The study was partly supported by Novartis Pharma GmbH (grant to Charité Universitätsmedizin Berlin (RS)); the funder was not involved in the study design, data collection, data analysis, manuscript preparation, and/or publication decisions. Furthermore, the study was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-WI 4760/2-1.

Author information

Correspondence to Robert Sabat.

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The authors declare that they have no conflict of interest.

Ethics statement

All skin samples were approved by the clinical institutional review board of the Charité University Hospital, Berlin, and written informed consent was obtained from all participants. The study was conducted according to the Declaration of Helsinki Principles.

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Witte, K., Jürchott, K., Christou, D. et al. Increased presence and differential molecular imprinting of transit amplifying cells in psoriasis. J Mol Med 98, 111–122 (2020). https://doi.org/10.1007/s00109-019-01860-3

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Keywords

  • Psoriasis
  • Keratinocytes
  • Transit amplifying cells
  • Methylome
  • Transcriptome
  • Integrated multiscale-omics
  • Epigenetic