Non-invasive characterization of human bone marrow stimulation and reconstitution by cell-free messenger RNA sequencing
Arkaitz Ibarra (),
Jiali Zhuang,
Yue Zhao,
Neeraj S. Salathia,
Vera Huang,
Alexander D. Acosta,
Jonathan Aballi,
Shusuke Toden,
Amy P. Karns,
Intan Purnajo,
Julianna R. Parks,
Lucy Guo,
James Mason,
Darren Sigal,
Tina S. Nova,
Stephen R. Quake and
Michael Nerenberg ()
Additional contact information
Arkaitz Ibarra: Molecular Stethoscope, Inc.
Jiali Zhuang: Molecular Stethoscope, Inc.
Yue Zhao: Molecular Stethoscope, Inc.
Neeraj S. Salathia: Molecular Stethoscope, Inc.
Vera Huang: Molecular Stethoscope, Inc.
Alexander D. Acosta: Molecular Stethoscope, Inc.
Jonathan Aballi: Molecular Stethoscope, Inc.
Shusuke Toden: Molecular Stethoscope, Inc.
Amy P. Karns: Molecular Stethoscope, Inc.
Intan Purnajo: Molecular Stethoscope, Inc.
Julianna R. Parks: Molecular Stethoscope, Inc.
Lucy Guo: Molecular Stethoscope, Inc.
James Mason: Scripps Green Hospital
Darren Sigal: Scripps Green Hospital
Tina S. Nova: Molecular Stethoscope, Inc.
Stephen R. Quake: Stanford University and Chan Zuckerberg Biohub
Michael Nerenberg: Molecular Stethoscope, Inc.
Nature Communications, 2020, vol. 11, issue 1, 1-11
Abstract:
Abstract 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.
Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14253-4
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DOI: 10.1038/s41467-019-14253-4
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