{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:07:10Z","timestamp":1792073230369,"version":"4.4.0"},"reference-count":51,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,9,29]]},"abstract":"<jats:p>The tuberous sclerosis complex (TSC)\u2013mammalian target of rapamycin (mTOR) pathway is a key regulator of cellular metabolism. We used conditional deletion of Tsc1 to address how quiescence is associated with the function of hematopoietic stem cells (HSCs). We demonstrate that Tsc1 deletion in the HSCs drives them from quiescence into rapid cycling, with increased mitochondrial biogenesis and elevated levels of reactive oxygen species (ROS). Importantly, this deletion dramatically reduced both hematopoiesis and self-renewal of HSCs, as revealed by serial and competitive bone marrow transplantation. In vivo treatment with an ROS antagonist restored HSC numbers and functions. These data demonstrated that the TSC\u2013mTOR pathway maintains the quiescence and function of HSCs by repressing ROS production. The detrimental effect of up-regulated ROS in metabolically active HSCs may explain the well-documented association between quiescence and the \u201cstemness\u201d of HSCs.<\/jats:p>","DOI":"10.1084\/jem.20081297","type":"journal-article","created":{"date-parts":[[2008,9,23]],"date-time":"2008-09-23T12:18:23Z","timestamp":1222172303000},"page":"2397-2408","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":652,"title":["TSC\u2013mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species"],"prefix":"10.1084","volume":"205","author":[{"given":"Chong","family":"Chen","sequence":"first","affiliation":[{"name":"1Program of Cell and Developmental Biology"},{"name":"2Division of Immunotherapy, Department of Surgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"2Division of Immunotherapy, Department of Surgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runhua","family":"Liu","sequence":"additional","affiliation":[{"name":"2Division of Immunotherapy, Department of Surgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuneo","family":"Ikenoue","sequence":"additional","affiliation":[{"name":"5Life Science Institute, University of Michigan Medical School and Comprehensive Cancer Center, Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-Liang","family":"Guan","sequence":"additional","affiliation":[{"name":"5Life Science Institute, University of Michigan Medical School and Comprehensive Cancer Center, Ann Arbor, MI 48109"},{"name":"6Department of Pharmacology and Cancer Center, University of California, San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"2Division of Immunotherapy, Department of Surgery"},{"name":"3Department of Internal Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Zheng","sequence":"additional","affiliation":[{"name":"2Division of Immunotherapy, Department of Surgery"},{"name":"4Department of Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2008,9,22]]},"reference":[{"key":"2023072516272445900_BIB1","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1182\/blood.V81.11.2844.2844","volume":"81","year":"1993","journal-title":"Blood."},{"key":"2023072516272445900_BIB2","first-page":"143","volume":"62","year":"1963","journal-title":"J. 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