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Cell Stem Cell. 2015 Jan 8;16(1):88-101. doi: 10.1016/j.stem.2014.11.005.

Single-cell transcriptome analysis reveals dynamic changes in lncRNA expression during reprogramming.

Author information

1
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: dkim@caltech.edu.
2
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
3
Center for Advanced Computing Research, California Institute of Technology, Pasadena, CA 91125, USA.
4
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
5
Illumina, Incorporated, San Diego, CA 92122, USA.
6
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: woldb@caltech.edu.

Abstract

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.

PMID:
25575081
PMCID:
PMC4291542
DOI:
10.1016/j.stem.2014.11.005
[Indexed for MEDLINE]
Free PMC Article

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