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

Author

Listed:
  • 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.)

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.

Suggested Citation

  • 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, 2020. "Non-invasive characterization of human bone marrow stimulation and reconstitution by cell-free messenger RNA sequencing," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14253-4
    DOI: 10.1038/s41467-019-14253-4
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    Cited by:

    1. Kate E. Stanley & Tatjana Jatsenko & Stefania Tuveri & Dhanya Sudhakaran & Lore Lannoo & Kristel Calsteren & Marie Borre & Ilse Parijs & Leen Coillie & Kris Bogaert & Rodrigo Almeida Toledo & Liesbeth, 2024. "Cell type signatures in cell-free DNA fragmentation profiles reveal disease biology," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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