Non-invasive characterization of human bone marrow stimulation and reconstitution by cell-free messenger RNA sequencing

被引：47

作者：

Ibarra, Arkaitz ^{[1
]}

Zhuang, Jiali ^{[1
]}

Zhao, Yue ^{[1
]}

Salathia, Neeraj S. ^{[1
]}

Huang, Vera ^{[1
]}

Acosta, Alexander D. ^{[1
]}

Aballi, Jonathan ^{[1
]}

Toden, Shusuke ^{[1
]}

Karns, Amy P. ^{[1
]}

Purnajo, Intan ^{[1
]}

Parks, Julianna R. ^{[1
]}

Guo, Lucy ^{[1
]}

Mason, James ^{[2
]}

Sigal, Darren ^{[2
]}

Nova, Tina S. ^{[1
]}

Quake, Stephen R. ^{[3
,4
,5
]}

Nerenberg, Michael ^{[1
]}

机构：

[1] Mol Stethoscope Inc, 3210 Merryfield Row, San Diego, CA 92121 USA

[2] Scripps Green Hosp, Scripps Clin Med Grp, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA

[3] Stanford Univ, Dept Bioengn, 318 Campus Dr, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Appl Phys, 318 Campus Dr, Stanford, CA 94305 USA

[5] Chan Zuckerberg Biohub, 318 Campus Dr, Stanford, CA 94305 USA

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

关键词：

FREE DNA; GENE-EXPRESSION; DIAGNOSIS; TRANSCRIPTOME; BIOMARKERS; ORIGIN; PLASMA; AGE;

D O I：

10.1038/s41467-019-14253-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Circulating cell-free mRNA (cf-mRNA) holds great promise as a non-invasive diagnostic biomarker. However, cf-mRNA composition and its potential clinical applications remain largely unexplored. Here we show, using Next Generation Sequencing-based profiling, that cf-mRNA is enriched in transcripts derived from the bone marrow compared to circulating cells. Further, longitudinal studies involving bone marrow ablation followed by hematopoietic stem cell transplantation in multiple myeloma and acute myeloid leukemia patients indicate that cf-mRNA levels reflect the transcriptional activity of bone marrow-resident hematopoietic lineages during bone marrow reconstitution. Mechanistically, stimulation of specific bone marrow cell populations in vivo using growth factor pharmacotherapy show that cf-mRNA reflects dynamic functional changes over time associated with cellular activity. Our results shed light on the biology of the circulating transcriptome and highlight the potential utility of cf-mRNA to non-invasively monitor bone marrow involved pathologies.

引用

页数：11

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