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.

中文翻译：

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无细胞信使RNA测序对人类骨髓刺激和重建的非侵入性表征。

循环无细胞mRNA（cf-mRNA）作为非侵入性诊断生物标志物具有广阔的前景。但是，cf-mRNA的组成及其潜在的临床应用仍未得到充分探索。在这里，我们显示，使用基于下一代测序的分析，与循环细胞相比，cf-mRNA富含源自骨髓的转录本。此外，在多发性骨髓瘤和急性髓细胞性白血病患者中涉及骨髓消融继而进行造血干细胞移植的纵向研究表明，cf-mRNA水平反映了骨髓重建过程中驻留于骨髓的造血谱系的转录活性。机械上，使用生长因子药物疗法对体内特定骨髓细胞群体的刺激显示，cf-mRNA反映了与细胞活性相关的动态功能变化。我们的研究结果揭示了循环转录组的生物学特性，并突出了cf-mRNA在无创监测骨髓病变中的潜在作用。