| Autor: |
Ibarra, Arkaitz, Zhao, Yue, Salathia, Neeraj, Zhuang, Jiali, Huang, Vera, Acosta, Alexander, Aballi, Jonathan, Toden, Shusuke, Karns, Amy, Purnajo, Intan, Parks, Julianna, Guo, Lucy, Mason, James, Sigal, Darren, Nova, Tina, Quake, Stephen, Nerenberg, Michael |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| DOI: |
10.1101/516666 |
| Popis: |
Circulating cell free mRNA (cf-mRNA) holds great promise as a non-invasive diagnostic biomarker. However, the biological origin of cf-mRNA is still not well understood, limiting the clinical applications of this technology. Here, we use the bone marrow (BM) and pharmacologic manipulation of its resident cells as a window to study the origin of cf-mRNA. Using NGS-based profiling, we show that cf-mRNA is enriched in transcripts derived from the BM compared to circulating cells. Further, BM ablation experiments followed by hematopoietic stem cell transplants in cancer patients show that cf-mRNA levels reflect the transcriptional activity of BM resident hematopoietic lineages during marrow reconstitution. Finally, by stimulating specific BM cell populations in vivo using growth factor therapeutics (i.e. EPO, G-CSF), we show that cf-mRNA reveals dynamic functional changes in growing cell types, suggesting that, unlike other cell-free nucleic acids, cf-mRNA is secreted from living cells, rather than exclusively from apoptotic cells. Our results shed new light on the biology of cf-mRNA and demonstrate its potential applications in clinical practice. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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