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Cell. 2019 Apr 4;177(2):463-477.e15. doi: 10.1016/j.cell.2019.02.018.

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

Author information

1
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
2
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
3
Department of Obstetrics, Gynecology, and Reproductive Sciences and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
4
Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Surgical Service, San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
5
Exosome Diagnostics, Inc., Waltham, MA 02451, USA.
6
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA; Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA.
7
Translational Nanobiology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
8
Gladstone Institutes, San Francisco, CA 94158, USA.
9
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
10
Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
11
Laboratory of Cell Biology, Center for Cancer Research, NIH, Bethesda, MD 20892, USA.
12
Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
13
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
14
Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; IBM T.J. Watson Research Center, IBM Research, Yorktown Heights, NY 10598, USA.
15
IBM T.J. Watson Research Center, IBM Research, Yorktown Heights, NY 10598, USA.
16
Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
17
Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Sema4, Stamford, CT 06902, USA.
18
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
19
Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
20
Department of Neurosurgery, Massachusetts General Hospital, Boston, MA 02114, USA.
21
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
22
Pacific Northwest Research Institute, Seattle, WA 98122, USA.
23
Department of Pathology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
24
School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
25
Neurogenomics, The Translational Genomics Research Institute (TGen), Phoenix, AZ 85004, USA.
26
Department of Transplantation, Mayo Clinic, Jacksonville, FL 32224, USA.
27
Department of Emergency Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
28
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA; Program in Computational Biology & Bioinformatics, Yale University, New Haven, CT 06520, USA; Department of Computer Science, Yale University, New Haven, CT 06520, USA.
29
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: amilosav@bcm.edu.

Abstract

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.

KEYWORDS:

ERCC; deconvolution; exRNA; exosomes; extracellular RNA; extracellular vesicles; lipoproteins; ribonucleoproteins

PMID:
30951672
PMCID:
PMC6616370
[Available on 2020-04-04]
DOI:
10.1016/j.cell.2019.02.018
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