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dc.contributor.authorQian, Pengxu
dc.contributor.authorHe, Xi C.
dc.contributor.authorPaulson, Ariel
dc.contributor.authorLi, Zhenrui
dc.contributor.authorTao, Fang
dc.contributor.authorPerry, John M.
dc.contributor.authorGuo, Fengli
dc.contributor.authorZhao, Meng
dc.contributor.authorZhi, Lei
dc.contributor.authorVenkatraman, Aparna
dc.contributor.authorHaug, Jeffrey S.
dc.contributor.authorParmely, Tari
dc.contributor.authorLi, Hua
dc.contributor.authorDobrowsky, Rick T.
dc.contributor.authorDing, Weng-Xing
dc.contributor.authorKono, Tomohiro
dc.contributor.authorFerguson-Smith, Anne C.
dc.contributor.authorLi, Linheng
dc.date.accessioned2017-09-15T16:23:34Z
dc.date.available2017-09-15T16:23:34Z
dc.date.issued2016-02
dc.identifier.citationQian, P., He, X. C., Paulson, A., Li, Z., Tao, F., Perry, J. M., … Li, L. (2016). The Dlk1-Gtl2 Locus Preserves LT-HSC Function by Inhibiting the PI3K-mTOR Pathway to Restrict Mitochondrial Metabolism. Cell Stem Cell, 18(2), 214–228. http://doi.org/10.1016/j.stem.2015.11.001en_US
dc.identifier.urihttp://hdl.handle.net/1808/24965
dc.description.abstractThe mammalian imprinted Dlk1-Gtl2 locus produces multiple non-coding RNAs (ncRNAs) from the maternally inherited allele, including the largest miRNA cluster in the mammalian genome. This locus has characterized functions in some types of stem cell, but its role in hematopoietic stem cells (HSCs) is unknown. Here, we show that the Dlk1-Gtl2 locus plays a critical role in preserving long-term repopulating HSCs (LT-HSCs). Through transcriptome profiling in 17 hematopoietic cell types, we found that ncRNAs expressed from the Dlk1-Gtl2 locus are predominantly enriched in fetal liver HSCs and the adult LT-HSC population and sustain long-term HSC functionality. Mechanistically, the miRNA mega-cluster within the Dlk1-Gtl2 locus suppresses the entire PI3K-mTOR pathway. This regulation in turn inhibits mitochondrial biogenesis and metabolic activity and protects LT-HSCs from excessive reactive oxygen species (ROS) production. Our data therefore show that the imprinted Dlk1-Gtl2 locus preserves LT-HSC function by restricting mitochondrial metabolism.en_US
dc.publisherElsevieren_US
dc.rightsCopyright © 2016 Elsevier Inc. All rights reserved.
dc.titleThe Dlk1-Gtl2 Locus Preserves LT-HSC Function by Inhibiting the PI3K-mTOR Pathway to Restrict Mitochondrial Metabolismen_US
dc.typeArticleen_US
kusw.kuauthorDobrowsky, Rick T.
kusw.kudepartmentPharmacology and Toxicologyen_US
dc.identifier.doi10.1016/j.stem.2015.11.001en_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC5545934en_US
dc.rights.accessrightsopenAccess


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