Cell Stem Cell
Volume 16, Issue 1, 8 January 2015, Pages 88-101
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Single-Cell Transcriptome Analysis Reveals Dynamic Changes in lncRNA Expression during Reprogramming

https://doi.org/10.1016/j.stem.2014.11.005Get rights and content
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Highlights

  • Hundreds of lncRNAs are dynamically expressed during reprogramming

  • Early reprogramming events include activation of Ras signaling pathways

  • lncRNAs activated during reprogramming can repress lineage-specific genes

  • lncRNAs activated in multiple reprogramming cell types regulate metabolism

Summary

Cellular reprogramming highlights the epigenetic plasticity of the somatic cell state. Long noncoding RNAs (lncRNAs) have emerging roles in epigenetic regulation, but their potential functions in reprogramming cell fate have been largely unexplored. We used single-cell RNA sequencing to characterize the expression patterns of over 16,000 genes, including 437 lncRNAs, during defined stages of reprogramming to pluripotency. Self-organizing maps (SOMs) were used as an intuitive way to structure and interrogate transcriptome data at the single-cell level. Early molecular events during reprogramming involved the activation of Ras signaling pathways, along with hundreds of lncRNAs. Loss-of-function studies showed that activated lncRNAs can repress lineage-specific genes, while lncRNAs activated in multiple reprogramming cell types can regulate metabolic gene expression. Our findings demonstrate that reprogramming cells activate defined sets of functionally relevant lncRNAs and provide a resource to further investigate how dynamic changes in the transcriptome reprogram cell state.

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