Variety of RNAs in Peripheral Blood Cells, Plasma, and Plasma Fractions

Savelyeva, Anna; Kuligina, Elena V.; Bariakin, D. N.; Kozlov, Vadim; Ryabchikova, E. I.; Richter, Vladimír; Semenov, Dmitry V.

doi:10.1155/2017/7404912

Cited by 51 publications

(37 citation statements)

References 38 publications

(53 reference statements)

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“…Of note, among the 14 immune-specific cell-free mRNAs selected by Ngo et al (55) as best predictors of gestational age at blood draw, 11 were also identified in our study, with CEACAM8, DEFA4, LTF, and MMP8 being among those with highest fold change. Although our results are somewhat consistent with those reported by Ngo et al (55), it should be noted that cellular and cell-free transcripts can follow different patterns in similar physiological and pathological processes (56).…”

Section: Transcriptomic Changes During Pregnancysupporting

confidence: 93%

The Cellular Transcriptome in the Maternal Circulation During Normal Pregnancy: A Longitudinal Study

et al. 2019

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Pregnancy represents a unique immunological state in which the mother adapts to tolerate the semi-allogenic conceptus; yet, the cellular dynamics in the maternal circulation are poorly understood. Using exon-level expression profiling of up to six longitudinal whole blood samples from 49 pregnant women, we undertook a systems biology analysis of the cellular transcriptome dynamics and its correlation with the plasma proteome. We found that: (1) chromosome 14 was the most enriched in transcripts differentially expressed throughout normal pregnancy; (2) the strongest expression changes followed three distinct longitudinal patterns, with genes related to host immune response (e.g., MMP8, DEFA1B, DEFA4, and LTF) showing a steady increase in expression from 10 to 40 weeks of gestation; (3) multiple biological processes and pathways related to immunity and inflammation were modulated during gestation; (4) genes changing with gestation were among those specific to T cells, B cells, CD71+ erythroid cells, natural killer cells, and endothelial cells, as defined based on the GNF Gene Expression Atlas; (5) the average expression of mRNA signatures of T cells, B cells, and erythroid cells followed unique patterns during gestation; (6) the correlation between mRNA and protein abundance was higher for mRNAs that were differentially expressed throughout gestation than for those that were not, and significant mRNA-protein correlations were observed for genes part of the T-cell signature. In summary, unique changes in immune-related genes were discovered by longitudinally assessing the cellular transcriptome in the maternal circulation throughout normal pregnancy, and positive correlations were noted between the cellular transcriptome and plasma proteome for specific genes/proteins. These findings provide insights into the immunobiology of normal pregnancy.

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Section: Transcriptomic Changes During Pregnancysupporting

confidence: 93%

The Cellular Transcriptome in the Maternal Circulation During Normal Pregnancy: A Longitudinal Study

et al. 2019

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“…At the beginning of this millennium, the first extracellular sncRNAs circulating in blood were discovered [21]. Since then, a wide variety of RNA species have been found in blood plasma [22,23] and its extracellular vesicles [24] by application of high-throughput sequencing. As diagnostic and therapeutic procedures shift from biopsies towards less invasive techniques, sncRNAs circulating in the blood become of particular interest as potential blood-based biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Circulating Small Noncoding RNAs Have Specific Expression Patterns in Plasma and Extracellular Vesicles in Myelodysplastic Syndromes and Are Predictive of Patient Outcome

Hruštincová

Krejčík

Kundrat

et al. 2020

Cells

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Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders with large heterogeneity at the clinical and molecular levels. As diagnostic procedures shift from bone marrow biopsies towards less invasive techniques, circulating small noncoding RNAs (sncRNAs) have become of particular interest as potential novel noninvasive biomarkers of the disease. We aimed to characterize the expression profiles of circulating sncRNAs of MDS patients and to search for specific RNAs applicable as potential biomarkers. We performed small RNA-seq in paired samples of total plasma and plasma-derived extracellular vesicles (EVs) obtained from 42 patients and 17 healthy controls and analyzed the data with respect to the stage of the disease, patient survival, response to azacitidine, mutational status, and RNA editing. Significantly higher amounts of RNA material and a striking imbalance in RNA content between plasma and EVs (more than 400 significantly deregulated sncRNAs) were found in MDS patients compared to healthy controls. Moreover, the RNA content of EV cargo was more homogeneous than that of total plasma, and different RNAs were deregulated in these two types of material. Differential expression analyses identified that many hematopoiesis-related miRNAs (e.g., miR-34a, miR-125a, and miR-150) were significantly increased in MDS and that miRNAs clustered on 14q32 were specifically increased in early MDS. Only low numbers of circulating sncRNAs were significantly associated with somatic mutations in the SF3B1 or DNMT3A genes. Survival analysis defined a signature of four sncRNAs (miR-1237-3p, U33, hsa_piR_019420, and miR-548av-5p measured in EVs) as the most significantly associated with overall survival (HR = 5.866, p < 0.001). In total plasma, we identified five circulating miRNAs (miR-423-5p, miR-126-3p, miR-151a-3p, miR-125a-5p, and miR-199a-3p) whose combined expression levels could predict the response to azacitidine treatment. In conclusion, our data demonstrate that circulating sncRNAs show specific patterns in MDS and that their expression changes during disease progression, providing a rationale for the potential clinical usefulness of circulating sncRNAs in MDS prognosis. However, monitoring sncRNA levels in total plasma or in the EV fraction does not reflect one another, instead, they seem to represent distinctive snapshots of the disease and the data should be interpreted circumspectly with respect to the type of material analyzed.

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“…Extracellular RNA content analysis of human biofluids and extracellular vesicles may provide insights into their biogenesis and reveal biomarkers for health and disease. There are currently four types of sequencing-based total RNA profiling of such challenging clinical samples: 1) the recent modified small RNA sequencing methods 8,9 , 2) the SOLiD total RNA sequening method 12 , 3) the Ion Proton method 13 and 4) TGIRT-sequencing using thermostable group II intron reverse transcriptases 5 . The SMARTer method assessed in our study adds a fifth promising method to the sequencing armory.…”

Section: Discussionmentioning

confidence: 99%

Performance assessment of total RNA sequencing of human biofluids and extracellular vesicles

Everaert

Helsmoortel

Decock

et al. 2019

Preprint

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RNA profiling has emerged as a powerful tool to investigate the biomarker potential of 18 human biofluids. However, despite enormous interest in extracellular nucleic acids, RNA 19 sequencing methods to quantify the total RNA content outside cells are rare. Here, we evaluate the 20 performance of the SMARTer Stranded Total RNA-Seq method in human platelet-rich plasma, 21 platelet-free plasma, urine, conditioned medium, and extracellular vesicles (EVs) from these 22 biofluids. We found the method to be accurate, precise, compatible with low-input volumes and 23 able to quantify a few thousand genes. We picked up distinct classes of RNA molecules, including 24 mRNA, lncRNA, circRNA, miscRNA and pseudogenes. Notably, the read distribution and gene 25 content drastically differ among biofluids. In conclusion, we are the first to show that the SMARTer 26 method can be used for unbiased unraveling of the complete transcriptome of a wide range of 27 biofluids and their extracellular vesicles. 28 30 31 2 of 15 1. Introduction 33All human biofluids contain a multitude of extracellular nucleic acids, harboring a wealth of 34 information about health and disease status. In addition to established non-invasive prenatal testing 35 of fetal nucleic acids in maternal plasma 1 , liquid biopsies have emerged as a novel powerful tool in 36 the battle against cancer 2 . Although in the past most attention was given to circulating DNA, its more 37 dynamic derivate extracellular RNA may provide additional layers of information. However, RNA 38 sequencing in biofluids is technically challenging. Low input amounts, large dynamic range, and 39 (partial) degradation of RNA hamper straightforward quantification. While sequencing of small 40 RNAs 3 and targeted or capture sequencing of longer RNAs 4 proved to be successful, studies using 41 total RNA sequencing on biofluids are rare. To date, only a few whole transcriptome profiling 42 attempts were made on urine, plasma or extracellular vesicles 5-9 , quantifying both polyadenylated 43 and non-polyadenylated RNA transcripts. However, all these methods suffer from one or more 44 limitations such as short fragment length, low amount of quantified genes or ribosomal RNA 45 contamination. 47The advantages of total RNA sequencing are plentiful. Indeed, detection is not limited to a set of pre-48 defined targets, nor to (3' ends of) polyadenylated RNAs. Next to polyadenylated mRNAs, various 49 other RNA biotypes including circular RNAs, histone RNAs, and a sizable fraction of long non-50 coding RNAs can be distinguished. In addition, the study of posttranscriptional regulation is possible 51 by comparing exonic and intronic reads 10 . Altogether, this generates a much more comprehensive 52 view of the transcriptome. 54Here we aimed to assess the performance of a strand-specific total RNA library preparation 55 method for different types of biofluids and derived extracellular vesicles (EVs). We applied the 56 method on platelet-rich plasma, platelet-free plasma, urine and conditioned medium from...

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Variety of RNAs in Peripheral Blood Cells, Plasma, and Plasma Fractions

Cited by 51 publications

References 38 publications

The Cellular Transcriptome in the Maternal Circulation During Normal Pregnancy: A Longitudinal Study

The Cellular Transcriptome in the Maternal Circulation During Normal Pregnancy: A Longitudinal Study

Circulating Small Noncoding RNAs Have Specific Expression Patterns in Plasma and Extracellular Vesicles in Myelodysplastic Syndromes and Are Predictive of Patient Outcome

Performance assessment of total RNA sequencing of human biofluids and extracellular vesicles

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