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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Vydané v:	Proceedings of the National Academy of Sciences - PNAS Ročník 111; číslo 20; s. 7361
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 20.05.2014
Predmet:	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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Abstract	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.
AbstractList	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.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. 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.
Author	Gawad, Charles Wyss-Coray, Tony Kerchner, Geoffrey A Koh, Winston Blumenfeld, Yair J Quake, Stephen R Pan, Wenying El-Sayed, Yasser Y Fan, H Christina
Author_xml	– sequence: 1 givenname: Winston surname: Koh fullname: Koh, Winston organization: Departments of Bioengineering and – sequence: 2 givenname: Wenying surname: Pan fullname: Pan, Wenying organization: Departments of Bioengineering and – sequence: 3 givenname: Charles surname: Gawad fullname: Gawad, Charles organization: Departments of Bioengineering and – sequence: 4 givenname: H Christina surname: Fan fullname: Fan, H Christina organization: Departments of Bioengineering and – sequence: 5 givenname: Geoffrey A surname: Kerchner fullname: Kerchner, Geoffrey A organization: Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305; and – sequence: 6 givenname: Tony surname: Wyss-Coray fullname: Wyss-Coray, Tony organization: Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305; and – sequence: 7 givenname: Yair J surname: Blumenfeld fullname: Blumenfeld, Yair J organization: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305 – sequence: 8 givenname: Yasser Y surname: El-Sayed fullname: El-Sayed, Yasser Y organization: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305 – sequence: 9 givenname: Stephen R surname: Quake fullname: Quake, Stephen R email: quake@stanford.edu organization: Departments of Bioengineering and quake@stanford.edu
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/24799715$$D View this record in MEDLINE/PubMed
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Snippet	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...
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SubjectTerms	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
Title	Noninvasive in vivo monitoring of tissue-specific global gene expression in humans
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