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. 2022 Mar 18;13(3):538.
doi: 10.3390/genes13030538.

Transcriptomics of Wet Skin Biopsies Predict Early Radiation-Induced Hematological Damage in a Mouse Model

Abdulnaser Alkhalil  1 , John Clifford  2 , Stacy Ann Miller  3 , Aarti Gautam  3 , Marti Jett  4 , Rasha Hammamieh  3 , Lauren T Moffatt  1   5   6 , Jeffrey W Shupp  1   5   6   7
Affiliations

Transcriptomics of Wet Skin Biopsies Predict Early Radiation-Induced Hematological Damage in a Mouse Model

Abdulnaser Alkhalil et al. Genes (Basel). .

Abstract

The lack of an easy and fast radiation-exposure testing method with a dosimetric ability complicates triage and treatment in response to a nuclear detonation, radioactive material release, or clandestine exposure. The potential of transcriptomics in radiation diagnosis and prognosis were assessed here using wet skin (blood/skin) biopsies obtained at hour 2 and days 4, 7, 21, and 28 from a mouse radiation model. Analysis of significantly differentially transcribed genes (SDTG; p ≤ 0.05 and FC ≥ 2) during the first post-exposure week identified the glycoprotein 6 (GP-VI) signaling, the dendritic cell maturation, and the intrinsic prothrombin activation pathways as the top modulated pathways with stable inactivation after lethal exposures (20 Gy) and intermittent activation after sublethal (1, 3, 6 Gy) exposure time points (TPs). Interestingly, these pathways were inactivated in the late TPs after sublethal exposure in concordance with a delayed deleterious effect. Modulated transcription of a variety of collagen types, laminin, and peptidase genes underlay the modulated functions of these hematologically important pathways. Several other SDTGs related to platelet and leukocyte development and functions were identified. These results outlined genetic determinants that were crucial to clinically documented radiation-induced hematological and skin damage with potential countermeasure applications.

Keywords: blood; genomics; hematocytes; radiation.

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Conflict of interest statement

No conflict of interest is declared.

Figures

Figure 1
Figure 1
Study design.
Figure 2
Figure 2
Pathway enrichment analysis of SDTGs (p ≤ 0.05 and FC ≥ 2) after exposure to the lethal dose (20 Gy). Pathways that did not pass filtration criteria (z-scores ≥ Abs 2 and −log p ≥ 1.3) at a time point are dotted.
Figure 3
Figure 3
Pathway enrichment analysis of SDTGs (p ≤ 0.05 and FC ≥ 2) in biopsies collected during the first week after exposure to lethal and sublethal IR doses.
Figure 4
Figure 4
Pathway enrichment analysis of SDTGs (p ≤ 0.05 and FC ≥ 2) from all TPs and IR doses (pathways z-scores > Abs 2.75 and −log p > 4 or p <0.0001). Pathways in red boxes contribute to hematological homeostasis.
Figure 5
Figure 5
Heatmap of the SDTGs (FC > 2 and −log p > 1.3) enriched to the IL-6 signaling pathway.
See this image and copyright information in PMC

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