{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:06:29Z","timestamp":1792073189838,"version":"4.4.0"},"reference-count":43,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,2,4]],"date-time":"2017-02-04T00:00:00Z","timestamp":1486166400000},"content-version":"vor","delay-in-days":369,"URL":"https:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell Stem Cell"],"published-print":{"date-parts":[[2016,2]]},"DOI":"10.1016\/j.stem.2015.11.001","type":"journal-article","created":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T12:46:52Z","timestamp":1448455612000},"page":"214-228","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":178,"title":["The Dlk1-Gtl2 Locus Preserves LT-HSC Function by Inhibiting the PI3K-mTOR Pathway to Restrict Mitochondrial Metabolism"],"prefix":"10.1016","volume":"18","author":[{"given":"Pengxu","family":"Qian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi\u00a0C.","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Paulson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenrui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John\u00a0M.","family":"Perry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengli","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Venkatraman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey\u00a0S.","family":"Haug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tari","family":"Parmely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick\u00a0T.","family":"Dobrowsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Xing","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Kono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u00a0C.","family":"Ferguson-Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.stem.2015.11.001_bib1","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1182\/blood-2013-10-530683","article-title":"Global discovery of erythroid long noncoding RNAs reveals novel regulators of red cell maturation","volume":"123","author":"Alvarez-Dominguez","year":"2014","journal-title":"Blood"},{"key":"10.1016\/j.stem.2015.11.001_bib2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: target recognition and regulatory functions","volume":"136","author":"Bartel","year":"2009","journal-title":"Cell"},{"key":"10.1016\/j.stem.2015.11.001_bib3","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1101\/gad.1841409","article-title":"Genomic imprinting: employing and avoiding epigenetic processes","volume":"23","author":"Bartolomei","year":"2009","journal-title":"Genes Dev."},{"key":"10.1016\/j.stem.2015.11.001_bib4","doi-asserted-by":"crossref","first-page":"5465","DOI":"10.1073\/pnas.1000834107","article-title":"Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion","volume":"107","author":"Beerman","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.stem.2015.11.001_bib5","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.stem.2009.11.014","article-title":"Intermediate-term hematopoietic stem cells with extended but time-limited reconstitution potential","volume":"6","author":"Benveniste","year":"2010","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.stem.2015.11.001_bib6","doi-asserted-by":"crossref","first-page":"e26410","DOI":"10.1371\/journal.pone.0026410","article-title":"Imprinted genes that regulate early mammalian growth are coexpressed in somatic stem cells","volume":"6","author":"Berg","year":"2011","journal-title":"PLoS ONE"},{"key":"10.1016\/j.stem.2015.11.001_bib7","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/383732a0","article-title":"Targeted ribose methylation of RNA in\u00a0vivo directed by tailored antisense RNA guides","volume":"383","author":"Cavaill\u00e9","year":"1996","journal-title":"Nature"},{"key":"10.1016\/j.stem.2015.11.001_bib8","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.cmet.2012.01.006","article-title":"Imprinted gene dosage is critical for the transition to independent life","volume":"15","author":"Charalambous","year":"2012","journal-title":"Cell Metab."},{"key":"10.1016\/j.stem.2015.11.001_bib9","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1084\/jem.20081297","article-title":"TSC-mTOR maintains quiescence and function of hematopoietic stem cells by\u00a0repressing mitochondrial biogenesis and reactive oxygen species","volume":"205","author":"Chen","year":"2008","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.stem.2015.11.001_bib10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/B978-0-12-416022-4.00002-0","article-title":"Hematopoietic stem cell development: an epigenetic journey","volume":"107","author":"Cullen","year":"2014","journal-title":"Curr. Top. Dev. Biol."},{"key":"10.1016\/j.stem.2015.11.001_bib11","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nature06322","article-title":"mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex","volume":"450","author":"Cunningham","year":"2007","journal-title":"Nature"},{"key":"10.1016\/j.stem.2015.11.001_bib12","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.tig.2008.03.011","article-title":"Genomic imprinting at the mammalian Dlk1-Dio3 domain","volume":"24","author":"da Rocha","year":"2008","journal-title":"Trends Genet."},{"key":"10.1016\/j.stem.2015.11.001_bib13","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1016\/j.celrep.2015.07.053","article-title":"PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells","volume":"12","author":"Das","year":"2015","journal-title":"Cell Rep."},{"key":"10.1016\/j.stem.2015.11.001_bib14","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/nrg3032","article-title":"Genomic imprinting: the emergence of an epigenetic paradigm","volume":"12","author":"Ferguson-Smith","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.stem.2015.11.001_bib15","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.pbi.2004.03.007","article-title":"Respiratory metabolism: glycolysis, the TCA cycle and mitochondrial electron transport","volume":"7","author":"Fernie","year":"2004","journal-title":"Curr. Opin. Plant Biol."},{"key":"10.1016\/j.stem.2015.11.001_bib16","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nature10229","article-title":"Postnatal loss of Dlk1 imprinting in stem cells and niche astrocytes regulates neurogenesis","volume":"475","author":"Ferr\u00f3n","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.stem.2015.11.001_bib17","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.stem.2008.01.017","article-title":"N-cadherin expression level distinguishes reserved versus primed states of hematopoietic stem cells","volume":"2","author":"Haug","year":"2008","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.stem.2015.11.001_bib18","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1111\/cas.12189","article-title":"Mechanistic \/ mammalian target protein of rapamycin signaling in hematopoietic stem cells and leukemia","volume":"104","author":"Hirao","year":"2013","journal-title":"Cancer Sci."},{"key":"10.1016\/j.stem.2015.11.001_bib19","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.1182\/blood-2007-05-087759","article-title":"A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche","volume":"110","author":"Jang","year":"2007","journal-title":"Blood"},{"key":"10.1016\/j.stem.2015.11.001_bib20","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.15252\/embj.201387038","article-title":"The miR-379\/miR-410 cluster at the imprinted Dlk1-Dio3 domain controls neonatal metabolic adaptation","volume":"33","author":"Labialle","year":"2014","journal-title":"EMBO J."},{"key":"10.1016\/j.stem.2015.11.001_bib21","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cell.2012.03.017","article-title":"mTOR signaling in growth control and disease","volume":"149","author":"Laplante","year":"2012","journal-title":"Cell"},{"key":"10.1016\/j.stem.2015.11.001_bib22","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.stem.2010.09.015","article-title":"mTOR activation induces tumor suppressors that inhibit leukemogenesis and deplete hematopoietic stem cells after Pten deletion","volume":"7","author":"Lee","year":"2010","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.stem.2015.11.001_bib23","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1126\/science.1180794","article-title":"Coexistence of quiescent and active adult stem cells in mammals","volume":"327","author":"Li","year":"2010","journal-title":"Science"},{"key":"10.1016\/j.stem.2015.11.001_bib24","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/ng1233","article-title":"Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlk1-Gtl2 imprinted cluster on mouse chromosome 12","volume":"35","author":"Lin","year":"2003","journal-title":"Nat. Genet."},{"key":"10.1016\/j.stem.2015.11.001_bib25","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1242\/dev.02726","article-title":"Differential regulation of imprinting in the murine embryo and placenta by the Dlk1-Dio3 imprinting control region","volume":"134","author":"Lin","year":"2007","journal-title":"Development"},{"key":"10.1016\/j.stem.2015.11.001_bib26","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.stem.2015.02.002","article-title":"Long non-coding RNAs control hematopoietic stem cell function","volume":"16","author":"Luo","year":"2015","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.stem.2015.11.001_bib27","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.cmet.2013.10.001","article-title":"mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation","volume":"18","author":"Morita","year":"2013","journal-title":"Cell Metab."},{"key":"10.1016\/j.stem.2015.11.001_bib28","doi-asserted-by":"crossref","first-page":"10302","DOI":"10.1073\/pnas.92.22.10302","article-title":"The purification and characterization of fetal liver hematopoietic stem cells","volume":"92","author":"Morrison","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.stem.2015.11.001_bib29","doi-asserted-by":"crossref","first-page":"4057","DOI":"10.1182\/blood.V87.10.4057.bloodjournal87104057","article-title":"Expression of murine CD38 defines a population of long-term reconstituting hematopoietic stem cells","volume":"87","author":"Randall","year":"1996","journal-title":"Blood"},{"key":"10.1016\/j.stem.2015.11.001_bib30","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/nature13255","article-title":"mTORC1 controls the adaptive transition of quiescent stem cells from G0 to G(Alert)","volume":"510","author":"Rodgers","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.stem.2015.11.001_bib31","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1101\/gr.2743304","article-title":"A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain","volume":"14","author":"Seitz","year":"2004","journal-title":"Genome Res."},{"key":"10.1016\/j.stem.2015.11.001_bib32","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.stem.2010.07.011","article-title":"The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche","volume":"7","author":"Simsek","year":"2010","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.stem.2015.11.001_bib33","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1242\/dev.081851","article-title":"MEF2A regulates the Gtl2-Dio3 microRNA mega-cluster to modulate WNT signaling in skeletal muscle regeneration","volume":"140","author":"Snyder","year":"2013","journal-title":"Development"},{"key":"10.1016\/j.stem.2015.11.001_bib34","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.stem.2011.09.010","article-title":"Metabolic regulation of hematopoietic stem cells in the hypoxic niche","volume":"9","author":"Suda","year":"2011","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.stem.2015.11.001_bib35","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1093\/hmg\/ddp108","article-title":"Deletion of Gtl2, imprinted non-coding RNA, with its differentially methylated region induces lethal parent-origin-dependent defects in mice","volume":"18","author":"Takahashi","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.stem.2015.11.001_bib36","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.stem.2012.10.011","article-title":"Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells","volume":"12","author":"Takubo","year":"2013","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.stem.2015.11.001_bib37","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.ygeno.2005.09.018","article-title":"High-resolution map and imprinting analysis of the Gtl2-Dnchc1 domain on mouse chromosome 12","volume":"87","author":"Tierling","year":"2006","journal-title":"Genomics"},{"key":"10.1016\/j.stem.2015.11.001_bib38","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nature12303","article-title":"Maternal imprinting at the H19-Igf2 locus maintains adult haematopoietic stem cell quiescence","volume":"500","author":"Venkatraman","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.stem.2015.11.001_bib39","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.cell.2008.10.048","article-title":"Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair","volume":"135","author":"Wilson","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.stem.2015.11.001_bib40","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1182\/blood-2004-06-2159","article-title":"Identification of Lin(-)Sca1(+)kit(+)CD34(+)Flt3- short-term hematopoietic stem cells capable of rapidly reconstituting and rescuing myeloablated transplant recipients","volume":"105","author":"Yang","year":"2005","journal-title":"Blood"},{"key":"10.1016\/j.stem.2015.11.001_bib41","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.stem.2011.07.007","article-title":"Lung stem cell self-renewal relies on BMI1-dependent control of expression at imprinted loci","volume":"9","author":"Zacharek","year":"2011","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.stem.2015.11.001_bib42","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nature04747","article-title":"PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention","volume":"441","author":"Zhang","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.stem.2015.11.001_bib43","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1242\/dev.045724","article-title":"Activation of paternally expressed genes and perinatal death caused by deletion of the Gtl2 gene","volume":"137","author":"Zhou","year":"2010","journal-title":"Development"}],"container-title":["Cell Stem Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1934590915004993?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1934590915004993?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T17:50:36Z","timestamp":1599846636000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1934590915004993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["S1934590915004993"],"URL":"https:\/\/doi.org\/10.1016\/j.stem.2015.11.001","relation":{},"ISSN":["1934-5909"],"issn-type":[{"value":"1934-5909","type":"print"}],"subject":[],"published":{"date-parts":[[2016,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The Dlk1-Gtl2 Locus Preserves LT-HSC Function by Inhibiting the PI3K-mTOR Pathway to Restrict Mitochondrial Metabolism","name":"articletitle","label":"Article Title"},{"value":"Cell Stem Cell","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.stem.2015.11.001","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"https:\/\/doi.org\/10.1016\/j.stem.2016.01.004","name":"associatedlink","label":"CrossRef DOI link to the associated document"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2016 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}