Transcriptomic Heterogeneity of Skin Across Different Anatomic Sites

Yan, Yicen; Tian, Jie; Wang, Yang; Li, Yurong; Zhang, Chong; Zhang, Shenxi; Lin, Pingping; Peng, Rui; Zhao, Chunxia; Liu, Zhuang; Lai, Binbin; Zhang, Liang; Zhang, Guohong; Li, Hang

doi:10.1016/j.jid.2022.08.053

Cited by 7 publications

(6 citation statements)

References 42 publications

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“…For instance, fibroblasts exhibit distinct gene expression patterns based on their positional identity in relation to the major anatomical axis 105 . This phenomenon in part explains the predisposition of different sites to different skin conditions 104 . Although several genes related to collagen synthesis and ECM were downregulated across all four MHU-2 experimental groups, some of these genes showed statistical significance in the dorsal group but not in the femoral group (Fig.…”

Section: Discussionmentioning

confidence: 95%

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Transcriptomics analysis reveals molecular alterations underpinning spaceflight dermatology

Cope,

Elsborg,

Demharter

et al. 2024

Commun Med

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Background Spaceflight poses a unique set of challenges to humans and the hostile spaceflight environment can induce a wide range of increased health risks, including dermatological issues. The biology driving the frequency of skin issues in astronauts is currently not well understood. Methods To address this issue, we used a systems biology approach utilizing NASA’s Open Science Data Repository (OSDR) on space flown murine transcriptomic datasets focused on the skin, biochemical profiles of 50 NASA astronauts and human transcriptomic datasets generated from blood and hair samples of JAXA astronauts, as well as blood samples obtained from the NASA Twins Study, and skin and blood samples from the first civilian commercial mission, Inspiration4. Results Key biological changes related to skin health, DNA damage & repair, and mitochondrial dysregulation are identified as potential drivers for skin health risks during spaceflight. Additionally, a machine learning model is utilized to determine gene pairings associated with spaceflight response in the skin. While we identified spaceflight-induced dysregulation, such as alterations in genes associated with skin barrier function and collagen formation, our results also highlight the remarkable ability for organisms to re-adapt back to Earth via post-flight re-tuning of gene expression. Conclusion Our findings can guide future research on developing countermeasures for mitigating spaceflight-associated skin damage.

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Section: Discussionmentioning

confidence: 95%

“…Skin has an anatomically heterogeneous gene expression profile 104 . For instance, fibroblasts exhibit distinct gene expression patterns based on their positional identity in relation to the major anatomical axis 105 .…”

Section: Discussionmentioning

confidence: 99%

Transcriptomics analysis reveals molecular alterations underpinning spaceflight dermatology

Cope,

Elsborg,

Demharter

et al. 2024

Commun Med

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“…Therefore, we adjusted for age and gender during differential expression testing and no strong differences have been found for the anatomical sites we used (i.e. trunk and extremities) 48 . In future studies, other mediators known to be upregulated in AD such as IL‐22 or IL‐31 may be studied in parallel or in addition to IL‐13 in 2D models to study if the in vitro signature of regulated genes is even closer to the in vivo situation as with IL‐13 alone.…”

Section: Discussionmentioning

confidence: 99%

Single‐cell RNA sequencing reveals 2D cytokine assay can model atopic dermatitis more accurately than immune‐competent 3D setup

Al,

Traidl,

Holzscheck

et al. 2024

Experimental Dermatology

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Modelling atopic dermatitis (AD) in vitro is paramount to understand the disease pathophysiology and identify novel treatments. Previous studies have shown that the Th2 cytokines IL‐4 and IL‐13 induce AD‐like features in keratinocytes in vitro. However, it has not been systematically researched whether the addition of Th2 cells, their supernatants or a 3D structure is superior to model AD compared to simple 2D cell culture with cytokines. For the first time, we investigated what in vitro option most closely resembles the disease in vivo based on single‐cell RNA sequencing data (scRNA‐seq) obtained from skin biopsies in a clinical study and published datasets of healthy and AD donors. In vitro models were generated with primary fibroblasts and keratinocytes, subjected to cytokine treatment or Th2 cell cocultures in 2D/3D. Gene expression changes were assessed using qPCR and Multiplex Immunoassays. Of all cytokines tested, incubation of keratinocytes and fibroblasts with IL‐4 and IL‐13 induced the closest in vivo‐like AD phenotype which was observed in the scRNA‐seq data. Addition of Th2 cells to fibroblasts failed to model AD due to the downregulation of ECM‐associated genes such as POSTN. While keratinocytes cultured in 3D showed better stratification than in 2D, changes induced with AD triggers did not better resemble AD keratinocyte subtypes observed in vivo. Taken together, our comprehensive study shows that the simple model using IL‐4 or IL‐13 in 2D most accurately models AD in fibroblasts and keratinocytes in vitro, which may aid the discovery of novel treatment options.

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“…Undisputably, variation exists in the transcriptome of skin from distinct anatomical sites ( 6 ) which may alter disease penetrance. None-the-less, once HS has progressed to late stages, differences in disease-driving tissue-specific transcriptomics are not yet described.…”

Section: Variation Of Transcriptome Among Various Anatomical Regions ...mentioning

confidence: 99%

Reply to Nebo et al.: Pathogenesis of advanced hidradenitis suppurativa: Are there differences based on anatomical location, gender, and race?

Jin,

Kashyap,

Haque

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Transcriptomic Heterogeneity of Skin Across Different Anatomic Sites

Cited by 7 publications

References 42 publications

Transcriptomics analysis reveals molecular alterations underpinning spaceflight dermatology

Transcriptomics analysis reveals molecular alterations underpinning spaceflight dermatology

Single‐cell RNA sequencing reveals 2D cytokine assay can model atopic dermatitis more accurately than immune‐competent 3D setup

Reply to Nebo et al.: Pathogenesis of advanced hidradenitis suppurativa: Are there differences based on anatomical location, gender, and race?

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