Single-cell transcriptomes in the heart: when every epigenome counts

Gromova, Tatiana; Gehred, Natalie; Vondriska, Thomas M.

doi:10.1093/cvr/cvac040

Cited by 3 publications

(1 citation statement)

References 127 publications

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“…These independent or combined "single" technologies have helped us not only to create a high-resolution SC type map of human tissues [127] and three-dimensional nuclear architecture, gene expression, and epigenetic modifications, [128] but also to assess and analyze immune cell differentiation, [129,130] to uncover cellular and molecular mechanisms and to discover new therapeutic targets for human diseases, [49,[131][132][133] in particular COVID-19 and CVDs, as well as to trace cancer progression. [134] It can be said that this is indeed a new "single" era of biomedicine and its current implications and research in both CVDs and COVID-19 [135][136][137][138][139][140][141][142][143][144][145][146][147][148][149][150] as well as others will definitely open a new beautiful future.…”

Section: Cavdmentioning

confidence: 99%

A new "single" era of biomedicine and implications in disease research

2023

J Bio-X Res

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Section: Cavdmentioning

confidence: 99%

A new "single" era of biomedicine and implications in disease research

2023

J Bio-X Res

View full text Add to dashboard Cite

show abstract

A diagnostic protein assay for differentiating follicular thyroid adenoma and carcinoma

Sun,

Wang,

et al. 2024

Preprint

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Differentiating follicular thyroid adenoma (FTA) from carcinoma (FTC) remains challenging due to similar histological features separate from invasion. In this study, we aim to develop and validate DNA and protein-based classifiers for FTA/FTC differentiation. We collected 2443 samples from 1568 patients across 24 centers and applied next-generation sequencing, as well as discovery and targeted proteomics. Machine learning models were developed and compared utilizing DNA and/or protein features. The discovery protein-based model (AUC 0.899) outperformed the gene-based model (AUC 0.670). Consequently, we generated a protein-based model with targeted mass spectrometry and further validated it in three independent testing sets. The 24-protein-based model achieved high performance in the retrospective sets (AUC 0.871 and 0.853) and the prospective fine-needle aspiration biopsies (AUC 0.781). The classifier notably illustrated a 95.7% negative predictive value for ruling out malignant nodules. This study offers a promising protein-based approach for differential diagnosis of FTA and FTC.

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Rapid onset fibrotic remodeling and ventricular dysfunction induced by phenylephrine involve targeted reprogramming of myocyte and fibroblast transcriptomes

Kimball,

Gromova,

Gehred

et al. 2024

Preprint

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Catecholamine dysregulation is a common feature of multiple acute and chronic cardiac conditions, including heart failure. To investigate the role of altered α-adrenergic stimulation on cardiac function, we developed a short-term exposure model, administering phenylephrine subcutaneously to mice for one week. Compared to vehicle-injected controls, phenylephrine-treated animals exhibited increased ejection fraction, decreased chamber size, diastolic dysfunction and ventricular hypertrophy in the absence of hypertension. Remarkably, these animals developed extensive fibrotic remodeling of the tissue that plateaued at 24 hours and myocyte hypertrophy localized to regions of fibrotic deposition after 3 days of treatment. Transcriptome analyses of purified myocyte and fibroblast populations from these hearts revealed an unexpected role for myocytes in the production of extracellular matrix. Comparison with other models of cardiac stress, including pressure overload hypertrophy and cytokine activation of fibroblasts, identified stimulus-specific transcriptional circuits associated with cardiac pathology. Given the rapid, robust fibrotic response that preceded myocyte hypertrophy, intercellular communication analyses were conducted to investigate fibroblast to myocyte signaling, identifying potential crosstalk between these cells. These studies thoroughly describe and phenotypically characterize a new model of short-term catecholamine stress and provide an atlas of transcriptional remodeling in myocytes and fibroblasts.

show abstract

Single-cell transcriptomes in the heart: when every epigenome counts

Cited by 3 publications

References 127 publications

A new "single" era of biomedicine and implications in disease research

A new "single" era of biomedicine and implications in disease research

A diagnostic protein assay for differentiating follicular thyroid adenoma and carcinoma

Rapid onset fibrotic remodeling and ventricular dysfunction induced by phenylephrine involve targeted reprogramming of myocyte and fibroblast transcriptomes

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