Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Purpose: Radiation cardiotoxicity (RC) is a clinically significant adverse effect of treatment for patients with thoracic malignancies. Clinical studies in lung cancer have indicated that heart substructures are not uniformly radiosensitive, and that dose to the heart base drives RC. In this study, we aimed to characterize late changes in gene expression using spatial transcriptomics in a mouse model of base regional radiosensitivity.
Methods And Materials: An aged female C57BL/6 mouse was irradiated with 16 Gy delivered to the cranial third of the heart using a 6 × 9 mm parallel opposed beam geometry on a small animal radiation research platform, and a second mouse was sham-irradiated. After echocardiography, whole hearts were collected at 30 weeks for spatial transcriptomic analysis to map gene expression changes occurring in different regions of the partially irradiated heart. Cardiac regions were manually annotated on the capture slides and the gene expression profiles compared across different regions.
Results: Ejection fraction was reduced at 30 weeks after a 16 Gy irradiation to the heart base, compared with the sham-irradiated controls. There were markedly more significant gene expression changes within the irradiated regions compared with nonirradiated regions. Variation was observed in the transcriptomic effects of radiation on different cardiac base structures (eg, between the right atrium [n = 86 dysregulated genes], left atrium [n = 96 dysregulated genes], and the vasculature [n = 129 dysregulated genes]). Disrupted biological processes spanned extracellular matrix as well as circulatory, neuronal, and contractility activities.
Conclusions: This is the first study to report spatially resolved gene expression changes in irradiated tissues. Examination of the regional radiation response in the heart can help to further our understanding of the cardiac base's radiosensitivity and support the development of actionable targets for pharmacologic intervention and biologically relevant dose constraints.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ijrobp.2022.08.031 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Integration of multi-omics resources reveals genetic features associated with environmental adaptation in the Wuzhishan pig genome.
J Therm Biol
September 2025
Hainan Key Laboratory of Tropical Animal Reproduction & Breeding and Epidemic Disease Research, School of Tropical Agriculture and Forestry, Hainan University, Haikou, 570228, China. Electronic address:
In light of the challenges posed by global climate change, the environmental adaptability of organisms is becoming increasingly important. The Wuzhishan (WZS) pig, tolerant to high heat and humidity, is an ideal model for genomic study. By characterizing its genome and assessing its genetic diversity and runs of homozygosity (ROH), we can gain insights into its current conservation status and genomic architecture.
View Article and Find Full Text PDFThe lncRNA ELDR suppresses tumorigenicity of AML by interfering with DNA replication and chromatin accessibility.
Blood Adv
September 2025
Institut de Recherches Cliniques de Montreal - IRCM, Montreal, Quebec, Canada.
Acute myeloid leukemia (AML) with rearrangement of the mixed lineage leukemia gene express MLL-AF9 fusion protein, a transcription factor that impairs differentiation and drives expansion of leukemic cells. We report here that the zinc finger protein GFI1 together with the histone methyltransferase LSD1 occupies the promoter and regulates expression of the lncRNA ELDR in the MLL-r AML cell line THP-1. Forced ELDR overexpression enhanced the growth inhibition of an LSD1i/ATRA combination treatment and reduced the capacity of these cells to generate leukemia in xenografts, leading to a longer leukemia-free survival.
View Article and Find Full Text PDFSREBP-mediated Signaling Restores Stem Cell Niche Properties in Human Lung Fibroblasts.
Am J Respir Cell Mol Biol
September 2025
INSERM U955 , Département de Physiologie, Hôpital Henri Mondor, AP-HP, DHU A-TVB France, Creteil, France;
Emphysema is characterized by chronic alveolar destruction. Lipofibroblasts (LIF) are crucial in the stem cell niche surrounding alveolar type II (AT2) cells and may contribute to alveolar regeneration. We aim to determine whether emphysema is associated with LIF reduction and whether Sterol regulatory binding protein (SREBP) activation promotes LIF differentiation and fibroblast stem cell niche properties.
View Article and Find Full Text PDFProtective Role of Apelin in a Mouse Model of Post-Intensive Care Syndrome.
Am J Respir Cell Mol Biol
September 2025
University of Toronto, Interdepartmental Division of Critical Care Medicine, Toronto, Ontario, Canada.
Post-Intensive Care Syndrome (PICS) is a serious condition involving physical weakness, depression, and cognitive impairment that develop during or after an intensive care unit (ICU) stay, often resulting in long-term declines in quality of life. Patients with acute respiratory distress syndrome (ARDS) and severe COVID-19 are at particularly high risk, yet the molecular mechanisms underlying PICS remain poorly understood. Here, we identify impaired Apelin-APJ signaling as a potential contributor to PICS pathogenesis via disruption of inter-organ homeostasis.
View Article and Find Full Text PDFSingle-cell transcriptome combined with genetic tracing reveals a roadmap of fibrosis formation during proliferative vitreoretinopathy.
Proc Natl Acad Sci U S A
September 2025
Department of Ophthalmology, Tianjin Medical University General Hospital, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Ocular Trauma, Laboratory of Molecular Ophthalmology, Tianjin Medical Univer
Ocular fibrosis, a severe consequence of excessive retinal wound healing, can lead to vision loss following retinal injury. Proliferative vitreoretinopathy (PVR), a common form of ocular fibrosis, is a major cause of blindness, characterized by the formation of extensive fibrous proliferative membranes. Understanding the cellular origins of PVR-associated fibroblasts (PAFs) is essential to decipher the mechanisms of ocular wound healing.
View Article and Find Full Text PDF