Genome-wide transcriptomics identifies an early preclinical signature of prion infection.
The clinical course of prion diseases is accurately predictable despite long latency periods, suggesting that prion pathogenesis is driven by precisely timed molecular events. We constructed a searchable genome-wide atlas of mRNA abundance and splicing alterations during the course of disease in pri...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-06-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008653 |
| _version_ | 1818582558357585920 |
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| author | Silvia Sorce Mario Nuvolone Giancarlo Russo Andra Chincisan Daniel Heinzer Merve Avar Manuela Pfammatter Petra Schwarz Mirzet Delic Micha Müller Simone Hornemann Despina Sanoudou Claudia Scheckel Adriano Aguzzi |
| author_facet | Silvia Sorce Mario Nuvolone Giancarlo Russo Andra Chincisan Daniel Heinzer Merve Avar Manuela Pfammatter Petra Schwarz Mirzet Delic Micha Müller Simone Hornemann Despina Sanoudou Claudia Scheckel Adriano Aguzzi |
| author_sort | Silvia Sorce |
| collection | DOAJ |
| description | The clinical course of prion diseases is accurately predictable despite long latency periods, suggesting that prion pathogenesis is driven by precisely timed molecular events. We constructed a searchable genome-wide atlas of mRNA abundance and splicing alterations during the course of disease in prion-inoculated mice. Prion infection induced PrP-dependent transient changes in mRNA abundance and processing already at eight weeks post inoculation, well ahead of any neuropathological and clinical signs. In contrast, microglia-enriched genes displayed an increase simultaneous with the appearance of clinical signs, whereas neuronal-enriched transcripts remained unchanged until the very terminal stage of disease. This suggests that glial pathophysiology, rather than neuronal demise, could be the final driver of disease. The administration of young plasma attenuated the occurrence of early mRNA abundance alterations and delayed signs in the terminal phase of the disease. The early onset of prion-induced molecular changes might thus point to novel biomarkers and potential interventional targets. |
| first_indexed | 2024-12-16T07:51:18Z |
| format | Article |
| id | doaj.art-3378ce74ef8f40b7a548373f25fdab25 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-16T07:51:18Z |
| publishDate | 2020-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-3378ce74ef8f40b7a548373f25fdab252022-12-21T22:38:51ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-06-01166e100865310.1371/journal.ppat.1008653Genome-wide transcriptomics identifies an early preclinical signature of prion infection.Silvia SorceMario NuvoloneGiancarlo RussoAndra ChincisanDaniel HeinzerMerve AvarManuela PfammatterPetra SchwarzMirzet DelicMicha MüllerSimone HornemannDespina SanoudouClaudia ScheckelAdriano AguzziThe clinical course of prion diseases is accurately predictable despite long latency periods, suggesting that prion pathogenesis is driven by precisely timed molecular events. We constructed a searchable genome-wide atlas of mRNA abundance and splicing alterations during the course of disease in prion-inoculated mice. Prion infection induced PrP-dependent transient changes in mRNA abundance and processing already at eight weeks post inoculation, well ahead of any neuropathological and clinical signs. In contrast, microglia-enriched genes displayed an increase simultaneous with the appearance of clinical signs, whereas neuronal-enriched transcripts remained unchanged until the very terminal stage of disease. This suggests that glial pathophysiology, rather than neuronal demise, could be the final driver of disease. The administration of young plasma attenuated the occurrence of early mRNA abundance alterations and delayed signs in the terminal phase of the disease. The early onset of prion-induced molecular changes might thus point to novel biomarkers and potential interventional targets.https://doi.org/10.1371/journal.ppat.1008653 |
| spellingShingle | Silvia Sorce Mario Nuvolone Giancarlo Russo Andra Chincisan Daniel Heinzer Merve Avar Manuela Pfammatter Petra Schwarz Mirzet Delic Micha Müller Simone Hornemann Despina Sanoudou Claudia Scheckel Adriano Aguzzi Genome-wide transcriptomics identifies an early preclinical signature of prion infection. PLoS Pathogens |
| title | Genome-wide transcriptomics identifies an early preclinical signature of prion infection. |
| title_full | Genome-wide transcriptomics identifies an early preclinical signature of prion infection. |
| title_fullStr | Genome-wide transcriptomics identifies an early preclinical signature of prion infection. |
| title_full_unstemmed | Genome-wide transcriptomics identifies an early preclinical signature of prion infection. |
| title_short | Genome-wide transcriptomics identifies an early preclinical signature of prion infection. |
| title_sort | genome wide transcriptomics identifies an early preclinical signature of prion infection |
| url | https://doi.org/10.1371/journal.ppat.1008653 |
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