Cell-Free DNA in Ischemic Stroke

Falcione, Sarina; Jickling, Glen C.

doi:10.1161/strokeaha.121.037525

Cited by 4 publications

(2 citation statements)

References 7 publications

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“…Moreover, they observed a trend of lower cfDNA levels in patients who had improved neurological status after tPA therapy. Grosse and colleagues [ 28 ] were able to show that higher levels of plasma cfDNA were associated with worse 90-day outcome and increased mortality after revascularization in stroke patients with endovascular therapy [ 57 , 58 ].…”

Section: Cell-free Dna In Strokementioning

confidence: 99%

The role of circulating cell-free DNA as an inflammatory mediator after stroke

2023

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Stroke is the second leading cause of death worldwide and a leading cause of disability. Clinical and experimental studies highlighted the complex role of the immune system in the pathophysiology of stroke. Ischemic brain injury leads to the release of cell-free DNA, a damage-associated molecular pattern, which binds to pattern recognition receptors on immune cells such as toll-like receptors and cytosolic inflammasome sensors. The downstream signaling cascade then induces a rapid inflammatory response. In this review, we are highlighting the characteristics of cell-free DNA and how these can affect a local as well as a systemic response after stroke. For this purpose, we screened literature on clinical studies investigating cell-free DNA concentration and properties after brain ischemia. We report the current understanding for mechanisms of DNA uptake and sensing in the context of post-stroke inflammation. Moreover, we compare possible treatment options targeting cell-free DNA, DNA-sensing pathways, and the downstream mediators. Finally, we describe clinical implications of this inflammatory pathway for stroke patients, open questions, and potential future research directions.

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Section: Cell-free Dna In Strokementioning

confidence: 99%

The role of circulating cell-free DNA as an inflammatory mediator after stroke

2023

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“…In cancer, tumor-derived cfDNA is leveraged to screen, diagnose, and monitor the treatment of patients with various cancer types 12 . Altered cfDNA profiles have also been noted in transplant rejection 13 , autoimmune disease 14 , infection 15 , 16 , myocardial infarction 17 , and stroke 18 , which may be the result of aberrant contributions from affected tissue types. To date, many strategies to trace cfDNA tissues-of-origin are limited by the need for genetic differences between the contributing tissue types (e.g., the fetal versus maternal genome, or mutated tumor DNA versus healthy tissue DNA).…”

Section: Introductionmentioning

confidence: 99%

Cell type signatures in cell-free DNA fragmentation profiles reveal disease biology

Stanley,

Jatsenko,

Tuveri

et al. 2024

Nat Commun

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Circulating cell-free DNA (cfDNA) fragments have characteristics that are specific to the cell types that release them. Current methods for cfDNA deconvolution typically use disease tailored marker selection in a limited number of bulk tissues or cell lines. Here, we utilize single cell transcriptome data as a comprehensive cellular reference set for disease-agnostic cfDNA cell-of-origin analysis. We correlate cfDNA-inferred nucleosome spacing with gene expression to rank the relative contribution of over 490 cell types to plasma cfDNA. In 744 healthy individuals and patients, we uncover cell type signatures in support of emerging disease paradigms in oncology and prenatal care. We train predictive models that can differentiate patients with colorectal cancer (84.7%), early-stage breast cancer (90.1%), multiple myeloma (AUC 95.0%), and preeclampsia (88.3%) from matched controls. Importantly, our approach performs well in ultra-low coverage cfDNA datasets and can be readily transferred to diverse clinical settings for the expansion of liquid biopsy.

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