Deciphering the Dynamic Molecular Program of Radiation-Induced Endothelial Senescence

Benadjaoud, Mohamed Amine; Soysouvanh, Frédéric; Tarlet, Georges; Paget, Vincent; Buard, Valérie; Andrade, Henrique Santos de; Morilla, Ian; Santos, M. Dos; Bertho, Annaïg; L’homme, Bruno; Gruel, Gaëtan; François, Agnès; Mondini, Michele; Deutsch, Éric; Guipaud, Olivier; Milliat, Fabien

doi:10.1016/j.ijrobp.2021.11.019

Cited by 14 publications

(7 citation statements)

References 40 publications

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“…Angiogenesis signals were generated to repair whatever gaps were created in the endothelial monolayer. Senescent signals were another way endothelial cells reacted to endure and survive the radiation damage 31 . Similar pathway differences have been observed by other groups in endothelial cells in response to radiation 27 , 30 , 31 .…”

Section: Discussionmentioning

confidence: 99%

“…The group identified alterations in angiogenesis in addition to DNA damage response, apoptosis, senescence, immune-response and fibrosis 30 . Radiation induced senescence signature with Interleukin-1 signaling pathway playing a key role was recently identified in cultured endothelial cells 31 . Bone marrow derived endothelial cells were investigated for transcriptional changes in response to 5 Gy total body irradiation (TBI) in mice and the group found that the effect peaked at 24 h but by 14 days post-radiation most changes had resolved 24 , 32 .…”

Section: Introductionmentioning

confidence: 99%

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Profiling mRNA, miRNA and lncRNA expression changes in endothelial cells in response to increasing doses of ionizing radiation

Chopra

Shankavaram

Bylicky

et al. 2022

Sci Rep

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Recent and past research have highlighted the importance of the endothelium in the manifestation of radiation injury. Our primary focus is on medical triage and management following whole body or partial-body irradiation. Here we investigated the usability of endothelial cells’ radiation response for biodosimetry applications. We profiled the transcriptome in cultured human endothelial cells treated with increasing doses of X-rays. mRNA expression changes were useful 24 h and 72 h post-radiation, microRNA and lncRNA expression changes were useful 72 h after radiation. More mRNA expressions were repressed than induced while more miRNA and lncRNA expressions were induced than repressed. These novel observations imply distinct radiation responsive regulatory mechanisms for coding and non-coding transcripts. It also follows how different RNA species should be explored as biomarkers for different time-points. Radiation-responsive markers which could classify no radiation (i.e., ‘0 Gy’) and dose-differentiating markers were also predicted. IPA analysis showed growth arrest-related processes at 24 h but immune response coordination at the 72 h post-radiation. Collectively, these observations suggest that endothelial cells have a precise dose and time-dependent response to radiation. Further studies in the laboratory are examining if these differences could be captured in the extracellular vesicles released by irradiated endothelial cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Profiling mRNA, miRNA and lncRNA expression changes in endothelial cells in response to increasing doses of ionizing radiation

Chopra

Shankavaram

Bylicky

et al. 2022

Sci Rep

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“…Clusters 0 and 5 presented increased differential gene expression of typical CEC markers, SLC4A11 , COL4A3 (Van den Bogerd et al, 2019), CDH2 (He et al, 2016), and ALCAM , compared to the other sequenced cells, suggesting these clusters were composed of therapy-grade CECs (Figure 2C and S4). Cluster 1 was identified as CECs transitioning towards a senescent phenotype due to the high differential expression of senescence markers such as MT2A (Malavolta et al, 2017), CDKN2A (p16) (Enomoto et al, 2006), and TAGLN (Benadjaoud et al, 2022) (Figure 2C and S4). Cluster 2 was composed of highly proliferative CECs expressing MKI67 (Sun and Kaufman, 2018), CENPF (Varis et al, 2006), and PTTG1 (Ersvær et al, 2020) (Figure 2C).…”

Section: Resultsmentioning

confidence: 99%

A Single-Cell RNA-Seq Analysis Unravels the Heterogeniety of Primary Cultured Human Corneal Endothelial Cells

Català

Gröen²,

LaPointe

et al. 2023

Preprint

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The primary culture of donor-derived human corneal endothelial cells (CECs) is a promising cell therapy. It confers the potential to treat multiple patients from a single donor, alleviating the global donor shortage. Nevertheless, this approach has limitations preventing its adoption, particularly culture protocols allow limited expansion of CECs and there is a lack of clear parameters to identify therapy-grade CECs. To address this limitation, a better understanding of the molecular changes arising from the primary culture of CECs is required. Using single-cell RNA sequencing on primary cultured CECs, we identify their variable transcriptomic fingerprint at the single cell level, provide a pseudo temporal reconstruction of the changes arising from primary culture, and suggest markers to assess the quality of primary CEC cultures. This research depicts a deep transcriptomic understanding of the cellular heterogeneity arising from the primary expansion of CECs and sets the basis for further improvement of culture protocols and therapies.

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“…This allowed the identification and selection of 11 additional genes potentially involved in the response to ionizing radiation. At last, we removed a few genes from the proteomic analysis to reach the number of 184 genes on the custom TLDA, and we added a few genes of interest based on our published work on radiation-induced endothelial-to-mesenchymal transition (EndoMT) (Mintet et al, 2015(Mintet et al, , 2017) (12 genes), endothelial senescence (Soysouvanh et al, 2020;Benadjaoud et al, 2022) (3 genes) and chemokines involved in the response to radiation (5 gens) (Tables S4-S9). Overall, after considering common genes between different datasets, this signature includes 184 genes.…”

Section: Establishment Of a Time-course Transcriptomic Signature Of I...mentioning

confidence: 99%

Comparing cellular response to two radiation treatments based on key features visualization

Arsenteva,

Guipaud,

Paget

et al. 2024

Preprint

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MotivationIn modern treatment by radiotherapy, different irradiation modalities can be used, potentially producing different amounts of adverse effects. The differences between these modalities are often studied via two-sample time course in vitro experiments. The resulting data may be of high complexity, in which case simple methods are unadapted for extracting all the relevant information.MethodsIn this article we introduce network-based tools for the visualization of the key statistical features, extracted from the data. For the key features extraction we utilize a statistical framework performing estimation, clustering with alignment of temporal omic fold changes originating from two-sample time course data.ResultsThe approach was applied to real transcriptomic data obtained with two different types of irradiation. The results were analyzed using biological literature and enrichment analysis, thus validating the robustness of the proposed tools as well as achieving better understanding of the differences in the impact of the treatments in question.Availability and implementationPython package freely available here:https://github.com/parsenteva/scanofc.Contactpolina.arsenteva@u-bourgogne.fr

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Deciphering the Dynamic Molecular Program of Radiation-Induced Endothelial Senescence

Cited by 14 publications

References 40 publications

Profiling mRNA, miRNA and lncRNA expression changes in endothelial cells in response to increasing doses of ionizing radiation

Profiling mRNA, miRNA and lncRNA expression changes in endothelial cells in response to increasing doses of ionizing radiation

A Single-Cell RNA-Seq Analysis Unravels the Heterogeniety of Primary Cultured Human Corneal Endothelial Cells

Comparing cellular response to two radiation treatments based on key features visualization

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