The NIH Extracellular RNA Communication Consortium

Ainsztein, Alexandra M.; Brooks, Philip J.; Dugan, Vivien G.; Ganguly, Aniruddha; Guo, Max; Howcroft, T. Kevin; Kelley, Christine A.; Kuo, Lili; Labosky, Patricia A.; Lenzi, Rebecca N.; McKie, George A.; Mohla, Suresh; Procaccini, Dena; Reilly, Matthew T.; Satterlee, John S.; Srinivas, Pothur R.; Church, Elizabeth Stansell; Sutherland, Margaret; Tagle, Danilo A.; Tucker, Jessica M.; Venkatachalam, Sundar

doi:10.3402/jev.v4.27493

Cited by 62 publications

(39 citation statements)

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“…The EVs can shuttle nucleic acid such as mRNA, RNA, and microRNA (miRNA) between cells. In fact, these circulatory RNAs, commonly called as extracellular RNA, play important role in health and disease with an immense potential to completely transform this field as reported by “The NIH Extracellular RNA consortium” . Proteins and lipoproteins including high‐ and low‐density lipoproteins are transported by non‐EV carriers in extracellular environment.…”

Section: Extracellular Secretory Vesicles Of Scsmentioning

confidence: 99%

Insights into cell‐free therapeutic approach: Role of stem cell “soup‐ernatant”

Raik

Kumar

Bhattacharyya

2017

Biotech and App Biochem

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Current advances in medicine have revolutionized the field of regenerative medicine dramatically with newly evolved therapies for repair or replacement of degenerating or injured tissues. Stem cells (SCs) can be harvested from different sources for clinical therapeutics, which include fetal tissues, umbilical cord blood, embryos, and adult tissues. SCs can be isolated and differentiated into desired lineages for tissue regeneration and cell replacement therapy. However, several loopholes need to be addressed properly before this can be extended for large-scale therapeutic application. These include a careful approach for patient safety during SC treatments and tolerance of recipients. SC treatments are associated with a number of risk factors and require successful integration and survival of transplanted cells in the desired microenvironment with concurrent tissue regeneration. Recent studies have focused on developing alternatives that can replace the cell-based therapy using paracrine factors. The development of stem "cell free" therapies can be devoted mainly to the use of soluble factors (secretome), extracellular vesicles, and mitochondrial transfer. The present review emphasizes on the paradigms related to the use of SC-based therapeutics and the potential applications of a cell-free approach as an alternative to cell-based therapy in the area of regenerative medicine.

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Section: Extracellular Secretory Vesicles Of Scsmentioning

confidence: 99%

Insights into cell‐free therapeutic approach: Role of stem cell “soup‐ernatant”

Raik

Kumar

Bhattacharyya

2017

Biotech and App Biochem

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“…The Extracellular RNA Communication Consortium (ERCC) (Ainsztein et al, 2015) aims to realize the potential of extracellular RNA (exRNA) as disease indicators and therapeutic molecules and to define the fundamental principles of their biogenesis, distribution, uptake, and function. In the context of this overall effort, the ERCC has developed the Extracellular RNA Atlas, a reference catalog of exRNAs present in human biofluids.…”

Section: Introductionmentioning

confidence: 99%

exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids

Murillo

Thistlethwaite

Rozowsky

et al. 2019

Cell

246

261

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Graphical Abstract Highlights d The exRNA Atlas provides access to human exRNA profiles and web-accessible tools d Atlas analysis reveals six exRNA cargo types present across five human biofluids d Five of the cargo types associate with specific vesicular and non-vesicular carriers d These findings and resources empower studies of extracellular RNA communication An extracellular RNA atlas from five human biofluids (serum, plasma, cerebrospinal fluid, saliva, and urine) reveals six extracellular RNA cargo types, including both vesicular and nonvesicular carriers. SUMMARY To develop a map of cell-cell communication mediated by extracellular RNA (exRNA), the NIH Extracellular RNA Communication Consortium created the exRNA Atlas resource (https://exrna-atlas.org). The Atlas version 4P1 hosts 5,309 exRNA-seq and exRNA qPCR profiles from 19 studies and a suite of analysis and visualization tools. To analyze variation between profiles, we apply computational deconvolution. The analysis leads to a model with six exRNA cargo types (CT1, CT2, CT3A, CT3B, CT3C, CT4), each detectable in multiple biofluids (serum, plasma, CSF, saliva, urine). Five of the cargo types associate with known vesicular and non-vesicular (lipoprotein and ribonucleoprotein) exRNA carriers. To validate utility of this model, we re-analyze an exercise response study by deconvolution to identify physiologically relevant response pathways that were not detected previously.To enable wide application of this model, as part of the exRNA Atlas resource, we provide tools for deconvolution and analysis of user-provided case-control studies.

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“…Among the exosomal molecules, proteins and miRNAs are currently the two major types that have been widely investigated for cancer diagnosis. Several exosome databases have been established to collect extensive exosomal proteins and miRNAs [40][41][42][43][44] . However, the feasibility of exosomal mRNAs as biomarker is still not well studied.…”

Section: Discussionmentioning

confidence: 99%

Cancer exosomes harbor diverse hypoxia-targeted mRNAs and contribute toward tumor angiogenesis

Zhang

Lim

Jiang

et al. 2020

Preprint

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Exosomes are extracellular vesicles of endosome origin secreted by various cells. The exosomal cargo, especially proteins and microRNAs, have been extensively investigated for their roles in intercellular communication and as biomarkers for clinical applications. However, the understanding of types and functions of exosomal mRNAs remains limited. Here, we evaluated the mRNAs of 61 hypoxia-targeted genes in exosomes by quantitative reverse transcription PCR (RT-qPCR). Among these 61 mRNAs, 14.8% of them were detected in the MCF10A-derived exosomes, 42.6% in the MCF7-derived exosomes, and 49.2% in the MDA-MB-231-derived exosomes, many of which are differentially regulated in response to hypoxic stress in a cell-line dependent manner. Consequently, 30 exosomal mRNAs are identified as cancer related biomarkers as they are present in cancer cell-derived exosomes and absent in MCF10A-derived exosomes. Co-culture of MDA-MB-231 cells with HUVECs shows uptake of MDA-MB-231 secreted exosomes by the Human umbilical vein endothelial cells (HUVECs). Subsequently, the cancer exosomal VEGFA mRNAs were translated within the HUVECs into proteins that promoted VEGFR-dependent angiogenesis. This finding provides novel insights into how cancer cells can directly contribute towards angiogenesis. RNA-seq also shows that cancer exosomes can upregulate epithelial-mesenchymal transition-related and metabolism-related genes. The transcripts of these genes are found present in the cancer exosomes, suggesting that the uptake of exosomal mRNAs at least partially contributed to the upregulation of the corresponding mRNAs. This study shows that cancer exosomes harbor diverse mRNAs, some of which can act as promising biomarkers as well as contribute towards reprogramming of recipient cells.

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The NIH Extracellular RNA Communication Consortium

Cited by 62 publications

References 0 publications

Insights into cell‐free therapeutic approach: Role of stem cell “soup‐ernatant”

Insights into cell‐free therapeutic approach: Role of stem cell “soup‐ernatant”

exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids

Cancer exosomes harbor diverse hypoxia-targeted mRNAs and contribute toward tumor angiogenesis

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