Human brain small extracellular vesicles contain selectively packaged, full-length mRNA
Summary: Brain cells release and take up small extracellular vesicles (sEVs) containing bioactive nucleic acids. sEV exchange is hypothesized to contribute to stereotyped spread of neuropathological changes in the diseased brain. We assess mRNA from sEVs of postmortem brain from non-diseased (ND) in...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-04-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724003899 |
| _version_ | 1827292094502273024 |
|---|---|
| author | Linnea S. Ransom Christine S. Liu Emily Dunsmore Carter R. Palmer Juliet Nicodemus Derya Ziomek Nyssa Williams Jerold Chun |
| author_facet | Linnea S. Ransom Christine S. Liu Emily Dunsmore Carter R. Palmer Juliet Nicodemus Derya Ziomek Nyssa Williams Jerold Chun |
| author_sort | Linnea S. Ransom |
| collection | DOAJ |
| description | Summary: Brain cells release and take up small extracellular vesicles (sEVs) containing bioactive nucleic acids. sEV exchange is hypothesized to contribute to stereotyped spread of neuropathological changes in the diseased brain. We assess mRNA from sEVs of postmortem brain from non-diseased (ND) individuals and those with Alzheimer’s disease (AD) using short- and long-read sequencing. sEV transcriptomes are distinct from those of bulk tissue, showing enrichment for genes including mRNAs encoding ribosomal proteins and transposable elements such as human-specific LINE-1 (L1Hs). AD versus ND sEVs show enrichment of inflammation-related mRNAs and depletion of synaptic signaling mRNAs. sEV mRNAs from cultured murine primary neurons, astrocytes, or microglia show similarities to human brain sEVs and reveal cell-type-specific packaging. Approximately 80% of neural sEV transcripts sequenced using long-read sequencing are full length. Motif analyses of sEV-enriched isoforms elucidate RNA-binding proteins that may be associated with sEV loading. Collectively, we show that mRNA in brain sEVs is intact, selectively packaged, and altered in disease. |
| first_indexed | 2024-04-24T12:50:42Z |
| format | Article |
| id | doaj.art-0b7d3a1cff9248ad86b9a7c9897bc007 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-24T12:50:42Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-0b7d3a1cff9248ad86b9a7c9897bc0072024-04-06T04:39:52ZengElsevierCell Reports2211-12472024-04-01434114061Human brain small extracellular vesicles contain selectively packaged, full-length mRNALinnea S. Ransom0Christine S. Liu1Emily Dunsmore2Carter R. Palmer3Juliet Nicodemus4Derya Ziomek5Nyssa Williams6Jerold Chun7Biomedical Sciences Graduate Program, School of Medicine, University of California, San Diego, La Jolla, CA, USA; Center for Genetic Disorders and Aging Research, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USACenter for Genetic Disorders and Aging Research, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USACenter for Genetic Disorders and Aging Research, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USACenter for Genetic Disorders and Aging Research, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USACenter for Genetic Disorders and Aging Research, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USACenter for Genetic Disorders and Aging Research, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USACenter for Genetic Disorders and Aging Research, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USACenter for Genetic Disorders and Aging Research, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA; Corresponding authorSummary: Brain cells release and take up small extracellular vesicles (sEVs) containing bioactive nucleic acids. sEV exchange is hypothesized to contribute to stereotyped spread of neuropathological changes in the diseased brain. We assess mRNA from sEVs of postmortem brain from non-diseased (ND) individuals and those with Alzheimer’s disease (AD) using short- and long-read sequencing. sEV transcriptomes are distinct from those of bulk tissue, showing enrichment for genes including mRNAs encoding ribosomal proteins and transposable elements such as human-specific LINE-1 (L1Hs). AD versus ND sEVs show enrichment of inflammation-related mRNAs and depletion of synaptic signaling mRNAs. sEV mRNAs from cultured murine primary neurons, astrocytes, or microglia show similarities to human brain sEVs and reveal cell-type-specific packaging. Approximately 80% of neural sEV transcripts sequenced using long-read sequencing are full length. Motif analyses of sEV-enriched isoforms elucidate RNA-binding proteins that may be associated with sEV loading. Collectively, we show that mRNA in brain sEVs is intact, selectively packaged, and altered in disease.http://www.sciencedirect.com/science/article/pii/S2211124724003899CP: NeuroscienceCP: Cell biology |
| spellingShingle | Linnea S. Ransom Christine S. Liu Emily Dunsmore Carter R. Palmer Juliet Nicodemus Derya Ziomek Nyssa Williams Jerold Chun Human brain small extracellular vesicles contain selectively packaged, full-length mRNA Cell Reports CP: Neuroscience CP: Cell biology |
| title | Human brain small extracellular vesicles contain selectively packaged, full-length mRNA |
| title_full | Human brain small extracellular vesicles contain selectively packaged, full-length mRNA |
| title_fullStr | Human brain small extracellular vesicles contain selectively packaged, full-length mRNA |
| title_full_unstemmed | Human brain small extracellular vesicles contain selectively packaged, full-length mRNA |
| title_short | Human brain small extracellular vesicles contain selectively packaged, full-length mRNA |
| title_sort | human brain small extracellular vesicles contain selectively packaged full length mrna |
| topic | CP: Neuroscience CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724003899 |
| work_keys_str_mv | AT linneasransom humanbrainsmallextracellularvesiclescontainselectivelypackagedfulllengthmrna AT christinesliu humanbrainsmallextracellularvesiclescontainselectivelypackagedfulllengthmrna AT emilydunsmore humanbrainsmallextracellularvesiclescontainselectivelypackagedfulllengthmrna AT carterrpalmer humanbrainsmallextracellularvesiclescontainselectivelypackagedfulllengthmrna AT julietnicodemus humanbrainsmallextracellularvesiclescontainselectivelypackagedfulllengthmrna AT deryaziomek humanbrainsmallextracellularvesiclescontainselectivelypackagedfulllengthmrna AT nyssawilliams humanbrainsmallextracellularvesiclescontainselectivelypackagedfulllengthmrna AT jeroldchun humanbrainsmallextracellularvesiclescontainselectivelypackagedfulllengthmrna |