Noninvasive in vivo monitoring of tissue-specific global gene expression in humans

Circulating cell-free RNA in the blood provides a potential window into the health, phenotype, and developmental programs of a variety of human organs. We used high-throughput methods of RNA analysis such as microarrays and next-generation sequencing to characterize the global landscape circulating...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS Jg. 111; H. 20; S. 7361
Hauptverfasser: Koh, Winston, Pan, Wenying, Gawad, Charles, Fan, H Christina, Kerchner, Geoffrey A, Wyss-Coray, Tony, Blumenfeld, Yair J, El-Sayed, Yasser Y, Quake, Stephen R
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 20.05.2014
Schlagworte:
Adult
Alzheimer Disease - blood
Apoptosis
Brain - embryology
Brain - metabolism
Female
Gene Expression Profiling - methods
Gene Expression Regulation, Developmental
Genomics - methods
High-Throughput Nucleotide Sequencing - methods
Humans
Neurodegenerative Diseases - physiopathology
Neurons - metabolism
Oligonucleotide Array Sequence Analysis
Pregnancy
RNA - blood
Time Factors
Transcriptome
cell-free nucleic acids
genomics
noninvasive diagnostics
ISSN:1091-6490, 1091-6490
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Zusammenfassung:Circulating cell-free RNA in the blood provides a potential window into the health, phenotype, and developmental programs of a variety of human organs. We used high-throughput methods of RNA analysis such as microarrays and next-generation sequencing to characterize the global landscape circulating RNA in a cohort of human subjects. By focusing on genes whose expression is highly specific to certain tissues, we were able to identify the relative contributions of these tissues to circulating RNA and to monitor changes in tissue development and health. As one application of this approach, we performed a longitudinal study on pregnant women and analyzed their combined cell-free RNA transcriptomes across all three trimesters of pregnancy and after delivery. In addition to the analysis of mRNA, we observed and characterized noncoding species such as long noncoding RNA and circular RNA transcripts whose presence had not been previously observed in human plasma. We demonstrate that it is possible to track specific longitudinal phenotypic changes in both the mother and the fetus and that it is possible to directly measure transcripts from a variety of fetal tissues in the maternal blood sample. We also studied the role of neuron-specific transcripts in the blood of healthy adults and those suffering from the neurodegenerative disorder Alzheimer's disease and showed that disease specific neural transcripts are present at increased levels in the blood of affected individuals. Characterization of the cell-free transcriptome in its entirety may thus provide broad insights into human health and development without the need for invasive tissue sampling.
Bibliographie:ObjectType-Article-1
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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.1405528111