title: Long non-coding RNAs control hematopoietic stem cell function.
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.
authors.affiliation: Stem Cells and Regenerative Medicine Center, Department of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.affiliation: Stem Cells and Regenerative Medicine Center, Department of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Mira
authors.initials: M
authors.lastname: Jeong
authors.affiliation: Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Deqiang
authors.initials: D
authors.lastname: Sun
authors.affiliation: Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Benjamin A T
authors.initials: BA
authors.lastname: Rodriguez
authors.affiliation: Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Stem Cells and Regenerative Medicine Center, Department of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Liubin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Stem Cells and Regenerative Medicine Center, Department of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Stem Cells and Regenerative Medicine Center, Department of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Kuanwei
authors.initials: K
authors.lastname: Sheng
authors.affiliation: Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Gretchen J
authors.initials: GJ
authors.lastname: Darlington
authors.affiliation: Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: wl1@bcm.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Stem Cells and Regenerative Medicine Center, Department of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: goodell@bcm.edu.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Goodell
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D001854:Bone Marrow Cells / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D000066673:Cell Self Renewal / Q000235:genetics; D002478:Cells, Cultured; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D059014:High-Throughput Nucleotide Sequencing; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; C000717967:DNMT3A protein, human; C075668:Tcf3 protein, mouse