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

66 Citations (Scopus)

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
Externally publishedYes

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Long Noncoding RNA
Hematopoietic Stem Cells
Binding Sites
Gene Expression
High-Throughput Nucleotide Sequencing
DNA Methylation
Regulator Genes
Transcriptome
Epigenomics
Transcription Factors

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Luo, M., Jeong, M., Sun, D., Park, H. J., Rodriguez, B. A. T., Xia, Z., ... 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

Long non-coding RNAs control hematopoietic stem cell function. / Luo, Min; Jeong, Mira; Sun, Deqiang; Park, Hyun Jung; Rodriguez, Benjamin A T; Xia, Zheng; Yang, Liubin; Zhang, Xiaotian; Sheng, Kuanwei; Darlington, Gretchen J.; Li, Wei; Goodell, Margaret A.

In: Cell Stem Cell, Vol. 16, No. 4, 02.04.2015, p. 426-438.

Research output: Contribution to journalArticle

Luo, M, Jeong, M, Sun, D, Park, HJ, Rodriguez, BAT, Xia, Z, Yang, L, Zhang, X, Sheng, K, Darlington, GJ, Li, W & Goodell, MA 2015, 'Long non-coding RNAs control hematopoietic stem cell function', Cell Stem Cell, vol. 16, no. 4, pp. 426-438. https://doi.org/10.1016/j.stem.2015.02.002
Luo M, Jeong M, Sun D, Park HJ, Rodriguez BAT, Xia Z et al. Long non-coding RNAs control hematopoietic stem cell function. Cell Stem Cell. 2015 Apr 2;16(4):426-438. https://doi.org/10.1016/j.stem.2015.02.002
Luo, Min ; Jeong, Mira ; Sun, Deqiang ; Park, Hyun Jung ; Rodriguez, Benjamin A T ; Xia, Zheng ; Yang, Liubin ; Zhang, Xiaotian ; Sheng, Kuanwei ; Darlington, Gretchen J. ; Li, Wei ; Goodell, Margaret A. / Long non-coding RNAs control hematopoietic stem cell function. In: Cell Stem Cell. 2015 ; Vol. 16, No. 4. pp. 426-438.
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