Long non-coding RNAs control hematopoietic stem cell function

Cell Stem Cell. 2015 Apr 2;16(4):426-38. doi: 10.1016/j.stem.2015.02.002. Epub 2015 Mar 12.

Abstract

Hematopoietic stem cells (HSCs) possess unique gene expression programs that enforce their identity and regulate lineage commitment. Long non-coding RNAs (lncRNAs) have emerged as important regulators of gene expression and cell fate decisions, although their functions in HSCs are unclear. Here we profiled the transcriptome of purified HSCs by deep sequencing and identified 323 unannotated lncRNAs. Comparing their expression in differentiated lineages revealed 159 lncRNAs enriched in HSCs, some of which are likely HSC specific (LncHSCs). These lncRNA genes share epigenetic features with protein-coding genes, including regulated expression via DNA methylation, and knocking down two LncHSCs revealed distinct effects on HSC self-renewal and lineage commitment. We mapped the genomic binding sites of one of these candidates and found enrichment for key hematopoietic transcription factor binding sites, especially E2A. Together, these results demonstrate that lncRNAs play important roles in regulating HSCs, providing an additional layer to the genetic circuitry controlling HSC function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Binding Sites / genetics
  • Bone Marrow Cells / physiology*
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • Cell Self Renewal / genetics
  • Cells, Cultured
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methylation / genetics
  • Epigenesis, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / genetics
  • Hematopoietic Stem Cells / physiology*
  • High-Throughput Nucleotide Sequencing
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / genetics

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Tcf3 protein, mouse
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA methyltransferase 3A

Associated data

  • GEO/GSE47817
  • GEO/GSE50775
  • GEO/GSE53928
  • GEO/GSE63276