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

Autor: Ibarra Arkaitz, Intan Purnajo, Tina S. Nova, Nerenberg Michael, Yue Zhao, Jiali Zhuang, Alexander D. Acosta, Lucy Guo, Jonathan Aballi, Julianna R. Parks, Neeraj Salathia, Amy P. Karns, Vera Huang, Shusuke Toden, Stephen R. Quake, Darren Sigal, James R. Mason
Rok vydání: 2019
Předmět:
0301 basic medicine
Myeloid
medicine.medical_treatment
General Physics and Astronomy
Hematopoietic stem cell transplantation
Bone Marrow Ablation
0302 clinical medicine
Bone Marrow
Granulocyte Colony-Stimulating Factor
Sequencing
Longitudinal Studies
lcsh:Science
Multiple myeloma
Aged
80 and over
Multidisciplinary
Molecular medicine
Hematopoietic Stem Cell Transplantation
High-Throughput Nucleotide Sequencing
RNA sequencing
Middle Aged
Haematopoiesis
Leukemia
Leukemia
Myeloid
Acute
medicine.anatomical_structure
Treatment Outcome
030220 oncology & carcinogenesis
Multiple Myeloma
Cell-Free Nucleic Acids
Adult
Science
Biology
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
Young Adult
Gene expression analysis
medicine
Biomarkers
Tumor
Humans
RNA
Messenger
Aged
Sequence Analysis
RNA
Growth factor
Gene Expression Profiling
General Chemistry
medicine.disease
Hematopoietic Stem Cells
030104 developmental biology
Cancer research
Feasibility Studies
lcsh:Q
Bone marrow
Zdroj: Nature Communications
Nature Communications, Vol 11, Iss 1, Pp 1-11 (2020)
ISSN: 2041-1723
Popis: 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.
Circulating cell-free mRNA holds great promise as a non-invasive diagnostic biomarker. Here the authors show that cell-free mRNA captures transcripts from the bone marrow and can be used to non-invasively monitor dynamic changes in bone marrow physiology.
Databáze: OpenAIRE
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