title: Single-cell transcriptome analysis reveals dynamic changes in lncRNA expression during reprogramming.
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.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: dkim@caltech.edu.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Georgi K
authors.initials: GK
authors.lastname: Marinov
authors.affiliation: Center for Advanced Computing Research, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Shirley
authors.initials: S
authors.lastname: Pepke
authors.affiliation: 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.
authors.forename: Zakary S
authors.initials: ZS
authors.lastname: Singer
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: He
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Williams
authors.affiliation: Illumina, Incorporated, San Diego, CA 92122, USA.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Schroth
authors.affiliation: 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.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Elowitz
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: woldb@caltech.edu.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Wold
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D050437:Genes, Developmental; D006410:Hematopoiesis / Q000235:genetics; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D039904:Pluripotent Stem Cells / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D059010:Single-Cell Analysis / Q000379:methods*; D059467:Transcriptome / Q000235:genetics*; D018631:ras Proteins / Q000378:metabolism
chemical_list: D062085:RNA, Long Noncoding; D018631:ras Proteins