RT Journal Article
SR Electronic
T1 Non-invasive characterization of human bone marrow by cell free messenger-RNA reveals response to growth factor stimulation and hematopoietic reconstitution after transplantation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 516666
DO 10.1101/516666
A1 Arkaitz Ibarra
A1 Yue Zhao
A1 Neeraj S. Salathia
A1 Jiali Zhuang
A1 Vera Huang
A1 Alexander D. Acosta
A1 Jonathan Aballi
A1 Shusuke Toden
A1 Amy P. Karns
A1 Intan Purnajo
A1 Julianna R. Parks
A1 Lucy Guo
A1 James Mason
A1 Darren Sigal
A1 Tina S. Nova
A1 Stephen R. Quake
A1 Michael Nerenberg
YR 2019
UL http://biorxiv.org/content/early/2019/01/10/516666.abstract
AB 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.