Long non-coding RNAs control hematopoietic stem cell function

Min Luo, Mira Jeong, Deqiang Sun, Hyun Jung Park, Benjamin A.T. Rodriguez, Zheng Xia, Liubin Yang, Xiaotian Zhang, Kuanwei Sheng, Gretchen J. Darlington, Wei Li, Margaret A. Goodell

Research output: Contribution to journalArticle

78 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)426-438
Number of pages13
JournalCell Stem Cell
Volume16
Issue number4
DOIs
StatePublished - Apr 2 2015

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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    Luo, M., Jeong, M., Sun, D., Park, H. J., Rodriguez, B. A. T., Xia, Z., Yang, L., Zhang, X., Sheng, K., Darlington, G. J., Li, W., & Goodell, M. A. (2015). Long non-coding RNAs control hematopoietic stem cell function. Cell Stem Cell, 16(4), 426-438. https://doi.org/10.1016/j.stem.2015.02.002