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Pre-symptomatic qPCR blood test based on Parkinson’s disease-specific angiogenin-derived transfer RNA fragments

ABSTRACT: Pre-symptomatic qPCR blood test based on Parkinson’s disease-specific angiogenin-derived transfer RNA fragments

PROVIDER: PRJNA1079205 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28046754.fastq.gz	Fastqsanger.gz
	SRR28046755.fastq.gz	Fastqsanger.gz
	SRR28046756.fastq.gz	Fastqsanger.gz
	SRR28046757.fastq.gz	Fastqsanger.gz
	SRR28046758.fastq.gz	Fastqsanger.gz

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Pre-symptomatic qPCR blood test based on Parkinson’s disease-specific angiogenin-derived transfer RNA fragments

Project description:Rapid, simple and reliable blood tests for Parkinson’s disease (PD) may enable pre-symptomatic diagnosis and facilitate disease-changing treatments. Here, we report escalated elevated levels of angiogenin-cleaved a disease specific group of nuclear genome-originated tRNA fragments (hereafter, PD-tRFs) carrying a unique seven-nucleotide motif in substantia nigra, cerebrospinal fluid and blood of PD patients. A blood test using RNA isolated from whole blood and dual multiplexl qPCR primers for PD-tRFs and mitochondrial-originated tRFs (MT-tRFs) successfully distinguished pre-symptomatic PD patients from controls, outperforming traditional clinical scoring (ROC-AUC of 0.86 vs. 0.73). Indicating relevance to disease symptoms, PD patients carrying GBA, SNCA or LRRK2 mutations presented elevated blood PD/MT-tRF ratios compared to mutations-carrying non-symptomatic individuals which indicates relevance to disease symptoms. Furthermore, PD-tRFs’ potential for ribosomal association predicted translational inhibition. Intriguingly, PD-tRFs levels declined both in patients’ blood following deep brain stimulation andas well as in in depolarized neuroblastoma cells where PD-tRFs presented transientlydepolirization impaired impacted ribosomal associations. Our findings facilitate a sensitive and accurate blood test for early PD.

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Human ANGIOGENIN is sufficient but not required for tRNA cleavage to generate tRNA fragments

Project description:To identify tRNA fragments regulated by angiogenin (ANG, Rnase 5), we sequenced 15-50nt small RNAs upon ANG overexpression and ANG knockout.

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Human ANGIOGENIN is sufficient but not required for tRNA cleavage to generate tRNA fragments

Project description:Human ANGIOGENIN is sufficient but not required for tRNA cleavage to generate tRNA fragments

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Angiogenin Released from ABCB5+ Stromal Precursors Improves Healing of Diabetic Wounds by Promoting Angiogenesis

Project description:Severe angiopathy is a major driver for diabetes associated secondary complications. Knowledge on underlying mechanisms essential for advanced therapies to attenuate these pathologies is limited. Injection of ABCB5+ stromal precursors (SPs) at the edge of non-healing diabetic wounds in a murine db/db model, closely mirroring human type II diabetes, profoundly accelerates wound closure. Strikingly, enhanced angiogenesis was substantially enforced by the release of the ribonuclease angiogenin from ABCB5+ SPs. This compensates for the profoundly reduced angiogenin expression in non-treated murine and human chronic diabetic wounds. Silencing of angiogenin in ABCB5+ SPs prior to injection significantly reduced angiogenesis, reduced numbers of M2 macrophages and delayed wound closure in diabetic db/db mice implying an unprecedented key role for angiogenin in tissue regeneration in diabetes. These data hold significant promise for further refining SPs-based therapies of non-healing diabetic foot ulcers and other pathologies with impaired angiogenesis.

2021-08-12 | GSE181881 | GEO

Differential Expression Spectrum of tRNA fragments in Alzheimer's Disease

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Project description:Cellular crosstalk in the tumor microenvironment (TME) is still largely uncharacterized, while it plays an essential role in shaping immunosuppression or anti-tumor response. Large-scale analyses are needed to better decipher cell-cell communication in cancer. In this work, we used original and publicly available single-cell RNA sequencing (scRNAseq) data to characterize in-depth the communication networks in human clear cell renal cell carcinoma (ccRCC). We identified 50 putative communication channels specifically used by cancer cells to interact with other cells, including two novel angiogenin-mediated interactions. Expression of angiogenin and its receptors was validated at the protein level in primary ccRCC. Mechanistically, angiogenin enhanced ccRCC cell line proliferation and down-regulated secretion of IL-6, IL-8, and MCP-1 proinflammatory molecules. This study provides novel biological insights into molecular mechanisms of ccRCC, and suggests angiogenin and its receptors as potential therapeutic targets in clear cell renal cancer.

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Project description:Stemming from preliminary results obtained by single cell-RNAseq we investigated by qPCR HSP and IFIT gene families in 27 LGLL patients (23 T-LGLL and 4 NK-LGLL), including 11 with neutropenia and/or thrombocytopenia and 16 asymptomatic for the disease. HSP90AA1 and HSPA1B, among HSP family and CD279 exhibit a significantly higher expression in CD3+ CD57+ sorted cells of symptomatic LGLL patients compared to asymptomatic patients and healthy controls. Also, monocytes derived from symptomatic LGLL patients express high levels of CCL3, CCL4 and CCL5 mRNA and of IL-1β, IL-6, TNF, and PD-L1 mRNA, thus confirming a pro-inflammatory cytokine profile reminiscent of a non-classical phenotype. HSP90AA1 and HSPA1B, among HSP family and CD279 exhibit a significantly higher expression in CD3+ CD57+ sorted cells of symptomatic LGLL patients compared to asymptomatic patients and healthy controls. Also, monocytes derived from symptomatic LGLL patients express high levels of CCL3, CCL4 and CCL5 mRNA and of IL-1β, IL-6, TNF, and PD-L1 mRNA, thus confirming a pro-inflammatory cytokine profile reminiscent of a non-classical phenotype. HSP90AA1 and HSPA1B, among HSP family and CD279 exhibit a significantly higher expression in CD3+ CD57+ sorted cells of symptomatic LGLL patients compared to asymptomatic patients and healthy controls. Also, monocytes derived from symptomatic LGLL patients express high levels of CCL3, CCL4 and CCL5 mRNA and of IL-1β, IL-6, TNF, and PD-L1 mRNA, thus confirming a pro-inflammatory cytokine profile reminiscent of a non-classical phenotype.

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