Toward a human brain extracellular vesicle atlas: Characteristics of extracellular vesicles from different brain regions, including small RNA and protein profiles

Author:

Huang Yiyao1ORCID,Arab Tanina1,Russell Ashley E.12,Mallick Emily R.1,Nagaraj Rajini3,Gizzie Evan3,Redding‐Ochoa Javier4,Troncoso Juan C.45,Pletnikova Olga46,Turchinovich Andrey78,Routenberg David A.3,Witwer Kenneth W.159ORCID

Affiliation:

1. Department of Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine Baltimore Maryland USA

2. Department of Biology School of Science Penn State Erie The Behrend College Erie Pennsylvania USA

3. Meso Scale Diagnostics LLC Rockville Maryland USA

4. Department of Pathology Johns Hopkins University School of Medicine Baltimore Maryland USA

5. Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland USA

6. Department of Pathology and Anatomical Sciences Jacobs School of Medicine and Biomedical Sciences University at Buffalo Buffalo New York USA

7. Division of Cancer Genome Research German Cancer Research Center (DKFZ) Heidelberg Germany

8. Heidelberg Biolabs GmbH Heidelberg Germany

9. The Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease Johns Hopkins University School of Medicine Baltimore Maryland USA

Abstract

AbstractExtracellular vesicles (EVs) are released from different cell types in the central nervous system (CNS) and play roles in regulating physiological and pathological functions. Although brain‐derived EVs (bdEVs) have been successfully collected from brain tissue, there is not yet a “bdEV Atlas” of EVs from different brain regions. To address this gap, we separated EVs from eight anatomical brain regions of a single individual and subsequently characterized them by count, size, morphology, and protein and RNA content. The greatest particle yield was from cerebellum, while the fewest particles were recovered from the orbitofrontal, postcentral gyrus, and thalamus regions. EV surface phenotyping indicated that CD81 and CD9 were more abundant than CD63 in all regions. Cell‐enriched surface markers varied between brain regions. For example, putative neuronal markers NCAM, CD271, and NRCAM were more abundant in medulla, cerebellum, and occipital regions, respectively. These findings, while restricted to tissues from a single individual, suggest that additional studies are warranted to provide more insight into the links between EV heterogeneity and function in the CNS.

Funder

National Institutes of Health

Publisher

Wiley

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