Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development
Transcript regulation is essential for cell function, and misregulation can lead to disease. Despite technologies to survey the transcriptome, we lack a comprehensive understanding of transcript kinetics, which limits quantitative biology. This is an acute challenge in embryonic development, where r...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-01-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715014916 |
| _version_ | 1811226237171924992 |
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| author | Nick D.L. Owens Ira L. Blitz Maura A. Lane Ilya Patrushev John D. Overton Michael J. Gilchrist Ken W.Y. Cho Mustafa K. Khokha |
| author_facet | Nick D.L. Owens Ira L. Blitz Maura A. Lane Ilya Patrushev John D. Overton Michael J. Gilchrist Ken W.Y. Cho Mustafa K. Khokha |
| author_sort | Nick D.L. Owens |
| collection | DOAJ |
| description | Transcript regulation is essential for cell function, and misregulation can lead to disease. Despite technologies to survey the transcriptome, we lack a comprehensive understanding of transcript kinetics, which limits quantitative biology. This is an acute challenge in embryonic development, where rapid changes in gene expression dictate cell fate decisions. By ultra-high-frequency sampling of Xenopus embryos and absolute normalization of sequence reads, we present smooth gene expression trajectories in absolute transcript numbers. During a developmental period approximating the first 8 weeks of human gestation, transcript kinetics vary by eight orders of magnitude. Ordering genes by expression dynamics, we find that “temporal synexpression” predicts common gene function. Remarkably, a single parameter, the characteristic timescale, can classify transcript kinetics globally and distinguish genes regulating development from those involved in cellular metabolism. Overall, our analysis provides unprecedented insight into the reorganization of maternal and embryonic transcripts and redefines our ability to perform quantitative biology. |
| first_indexed | 2024-04-12T09:21:35Z |
| format | Article |
| id | doaj.art-742bb556a93348a2ad7d4a46ecc74cdc |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-12T09:21:35Z |
| publishDate | 2016-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-742bb556a93348a2ad7d4a46ecc74cdc2022-12-22T03:38:38ZengElsevierCell Reports2211-12472016-01-0114363264710.1016/j.celrep.2015.12.050Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in DevelopmentNick D.L. Owens0Ira L. Blitz1Maura A. Lane2Ilya Patrushev3John D. Overton4Michael J. Gilchrist5Ken W.Y. Cho6Mustafa K. Khokha7The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway Mill Hill, London NW7 1AA, UKDepartment of Developmental and Cell Biology, University of California, Irvine, CA 92697 USAProgram in Vertebrate Developmental Biology, Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USAThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway Mill Hill, London NW7 1AA, UKDepartment of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USAThe Francis Crick Institute, Mill Hill Laboratory, The Ridgeway Mill Hill, London NW7 1AA, UKDepartment of Developmental and Cell Biology, University of California, Irvine, CA 92697 USAProgram in Vertebrate Developmental Biology, Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USATranscript regulation is essential for cell function, and misregulation can lead to disease. Despite technologies to survey the transcriptome, we lack a comprehensive understanding of transcript kinetics, which limits quantitative biology. This is an acute challenge in embryonic development, where rapid changes in gene expression dictate cell fate decisions. By ultra-high-frequency sampling of Xenopus embryos and absolute normalization of sequence reads, we present smooth gene expression trajectories in absolute transcript numbers. During a developmental period approximating the first 8 weeks of human gestation, transcript kinetics vary by eight orders of magnitude. Ordering genes by expression dynamics, we find that “temporal synexpression” predicts common gene function. Remarkably, a single parameter, the characteristic timescale, can classify transcript kinetics globally and distinguish genes regulating development from those involved in cellular metabolism. Overall, our analysis provides unprecedented insight into the reorganization of maternal and embryonic transcripts and redefines our ability to perform quantitative biology.http://www.sciencedirect.com/science/article/pii/S2211124715014916 |
| spellingShingle | Nick D.L. Owens Ira L. Blitz Maura A. Lane Ilya Patrushev John D. Overton Michael J. Gilchrist Ken W.Y. Cho Mustafa K. Khokha Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development Cell Reports |
| title | Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development |
| title_full | Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development |
| title_fullStr | Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development |
| title_full_unstemmed | Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development |
| title_short | Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development |
| title_sort | measuring absolute rna copy numbers at high temporal resolution reveals transcriptome kinetics in development |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715014916 |
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