TY - JOUR
T1 - Long non-coding RNAs control hematopoietic stem cell function
AU - Luo, Min
AU - Jeong, Mira
AU - Sun, Deqiang
AU - Park, Hyun Jung
AU - Rodriguez, Benjamin A.T.
AU - Xia, Zheng
AU - Yang, Liubin
AU - Zhang, Xiaotian
AU - Sheng, Kuanwei
AU - Darlington, Gretchen J.
AU - Li, Wei
AU - Goodell, Margaret A.
N1 - Funding Information:
This work was supported by NIH grants 5T32AI007495, AG036562, AG28865, CA126752, DK092883, and DK084259; by CPRIT grant RP110028; by the Samuel Waxman Cancer Research Foundation; and by the Edward P. Evans Foundation. W.L. was supported by CPRIT grants RP110471 and RP150292 and NIH grant R01HG007538. We thank the Cytometry and Cell Sorting (grants AI036211, CA125123, and RR024574), the Genomic and RNA Profiling (grant CA125123), and Integrated Microscopy (grants HD007495, DK56338, and CA125123) cores at Baylor College of Medicine.
Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/4/2
Y1 - 2015/4/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.stem.2015.02.002
DO - 10.1016/j.stem.2015.02.002
M3 - Article
C2 - 25772072
AN - SCOPUS:84926260800
SN - 1934-5909
VL - 16
SP - 426
EP - 438
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 4
ER -