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High resolution temporal transcriptomics of mouse embryoid body development reveals complex expression dynamics of coding and noncoding loci.

  • Gloss BS Garvan Institute of Medical Research, Sydney, Australia.
  • Signal B Garvan Institute of Medical Research, Sydney, Australia.
  • Cheetham SW The Gurdon Institute and Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
  • Gruhl F Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
  • Kaczorowski DC Garvan Institute of Medical Research, Sydney, Australia.
  • Perkins AC Mater-UQ Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Australia.
  • Dinger ME Garvan Institute of Medical Research, Sydney, Australia. m.dinger@garvan.org.au.
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  • 2017-07-29
Published in:
  • Scientific reports. - 2017
Alternative Splicing
Animals
Cell Differentiation
Chromosome Mapping
Embryoid Bodies
Gene Expression Profiling
Gene Expression Regulation, Developmental
Mice
Molecular Sequence Annotation
Mouse Embryonic Stem Cells
Open Reading Frames
Promoter Regions, Genetic
RNA, Long Noncoding
Time Factors
Transcription Factors
Transcriptome
English Cellular responses to stimuli are rapid and continuous and yet the vast majority of investigations of transcriptional responses during developmental transitions typically use long interval time courses; limiting the available interpretive power. Moreover, such experiments typically focus on protein-coding transcripts, ignoring the important impact of long noncoding RNAs. We therefore evaluated coding and noncoding expression dynamics at unprecedented temporal resolution (6-hourly) in differentiating mouse embryonic stem cells and report new insight into molecular processes and genome organization. We present a highly resolved differentiation cascade that exhibits coding and noncoding transcriptional alterations, transcription factor network interactions and alternative splicing events, little of which can be resolved by long-interval developmental time-courses. We describe novel short lived and cycling patterns of gene expression and dissect temporally ordered gene expression changes in response to transcription factors. We elucidate patterns in gene co-expression across the genome, describe asynchronous transcription at bidirectional promoters and functionally annotate known and novel regulatory lncRNAs. These findings highlight the complex and dynamic molecular events underlying mammalian differentiation that can only be observed though a temporally resolved time course.
Language
  • English
Open access status
gold
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Persistent URL
https://sonar.ch/global/documents/78706
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