1 Ocak 2019 Dergi makalesi Açık Erişim

Cheng, Chia-Wei; Biton, Moshe; Haber, Adam L.; Gunduz, Nuray; Eng, George; Gaynor, Liam T.; Tripathi, Surya; Calibasi-Koca, Gizem; Rickelt, Steffen; Butty, Vincent L.; Moreno-Serrano, Marta; Iqbal, Ameena M.; Bauer-Rowe, Khristian E.; Imada, Shinya; Ulutas, Mehmet Sefa; Mylonas, Constantine; Whary, Mark T.; Levine, Stuart S.; Basbinar, Yasemin; Hynes, Richard O.; Hynes, Richard O.

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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/72519</identifier>
  <creators>
    <creator>
      <creatorName>Cheng, Chia-Wei</creatorName>
      <givenName>Chia-Wei</givenName>
      <familyName>Cheng</familyName>
      <affiliation>MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA</affiliation>
    </creator>
    <creator>
      <creatorName>Biton, Moshe</creatorName>
      <givenName>Moshe</givenName>
      <familyName>Biton</familyName>
    </creator>
    <creator>
      <creatorName>Haber, Adam L.</creatorName>
      <givenName>Adam L.</givenName>
      <familyName>Haber</familyName>
      <affiliation>Broad Inst Harvard &amp; MIT, Klarman Cell Observ, Cambridge, MA 02142 USA</affiliation>
    </creator>
    <creator>
      <creatorName>Gunduz, Nuray</creatorName>
      <givenName>Nuray</givenName>
      <familyName>Gunduz</familyName>
    </creator>
    <creator>
      <creatorName>Eng, George</creatorName>
      <givenName>George</givenName>
      <familyName>Eng</familyName>
    </creator>
    <creator>
      <creatorName>Gaynor, Liam T.</creatorName>
      <givenName>Liam T.</givenName>
      <familyName>Gaynor</familyName>
      <affiliation>Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA</affiliation>
    </creator>
    <creator>
      <creatorName>Tripathi, Surya</creatorName>
      <givenName>Surya</givenName>
      <familyName>Tripathi</familyName>
      <affiliation>MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA</affiliation>
    </creator>
    <creator>
      <creatorName>Calibasi-Koca, Gizem</creatorName>
      <givenName>Gizem</givenName>
      <familyName>Calibasi-Koca</familyName>
    </creator>
    <creator>
      <creatorName>Rickelt, Steffen</creatorName>
      <givenName>Steffen</givenName>
      <familyName>Rickelt</familyName>
      <affiliation>MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA</affiliation>
    </creator>
    <creator>
      <creatorName>Butty, Vincent L.</creatorName>
      <givenName>Vincent L.</givenName>
      <familyName>Butty</familyName>
      <affiliation>MIT, Dept Biol, BioMicro Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA</affiliation>
    </creator>
    <creator>
      <creatorName>Moreno-Serrano, Marta</creatorName>
      <givenName>Marta</givenName>
      <familyName>Moreno-Serrano</familyName>
      <affiliation>MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA</affiliation>
    </creator>
    <creator>
      <creatorName>Iqbal, Ameena M.</creatorName>
      <givenName>Ameena M.</givenName>
      <familyName>Iqbal</familyName>
      <affiliation>MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA</affiliation>
    </creator>
    <creator>
      <creatorName>Bauer-Rowe, Khristian E.</creatorName>
      <givenName>Khristian E.</givenName>
      <familyName>Bauer-Rowe</familyName>
      <affiliation>MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA</affiliation>
    </creator>
    <creator>
      <creatorName>Imada, Shinya</creatorName>
      <givenName>Shinya</givenName>
      <familyName>Imada</familyName>
    </creator>
    <creator>
      <creatorName>Ulutas, Mehmet Sefa</creatorName>
      <givenName>Mehmet Sefa</givenName>
      <familyName>Ulutas</familyName>
    </creator>
    <creator>
      <creatorName>Mylonas, Constantine</creatorName>
      <givenName>Constantine</givenName>
      <familyName>Mylonas</familyName>
      <affiliation>MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA</affiliation>
    </creator>
    <creator>
      <creatorName>Whary, Mark T.</creatorName>
      <givenName>Mark T.</givenName>
      <familyName>Whary</familyName>
      <affiliation>MIT, Dept Biol Engn, Div Comparat Med, 77 Massachusetts Ave, Cambridge, MA 02139 USA</affiliation>
    </creator>
    <creator>
      <creatorName>Levine, Stuart S.</creatorName>
      <givenName>Stuart S.</givenName>
      <familyName>Levine</familyName>
      <affiliation>MIT, Dept Biol, BioMicro Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA</affiliation>
    </creator>
    <creator>
      <creatorName>Basbinar, Yasemin</creatorName>
      <givenName>Yasemin</givenName>
      <familyName>Basbinar</familyName>
      <affiliation>Dokuz Eylul Univ, Inst Oncol, Dept Translat Oncol, Izmir, Turkey</affiliation>
    </creator>
    <creator>
      <creatorName>Hynes, Richard O.</creatorName>
      <givenName>Richard O.</givenName>
      <familyName>Hynes</familyName>
    </creator>
    <creator>
      <creatorName>Hynes, Richard O.</creatorName>
      <givenName>Richard O.</givenName>
      <familyName>Hynes</familyName>
    </creator>
  </creators>
  <titles>
    <title>Ketone Body Signaling Mediates Intestinal Stem Cell Homeostasis And Adaptation To Diet</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2019</publicationYear>
  <dates>
    <date dateType="Issued">2019-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/72519</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1016/j.cell.2019.07.048</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://www.opendefinition.org/licenses/cc-by">Creative Commons Attribution</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">Little is known about how metabolites couple tissuespecific stem cell function with physiology. Here we show that, in the mammalian small intestine, the expression of Hmgcs2 (3-hydroxy-3-methylglutarylCoA synthetase 2), the gene encoding the ratelimiting enzyme in the production of ketone bodies, including beta-hydroxybutyrate (beta OHB), distinguishes self-renewing Lgr5(+) stem cells (ISCs) from differentiated cell types. Hmgcs2 loss depletes beta OHB levels in Lgr5(+) ISCs and skews their differentiation toward secretory cell fates, which can be rescued by exogenous beta OHB and class I histone deacetylase (HDAC) inhibitor treatment. Mechanistically, beta OHB acts by inhibiting HDACs to reinforce Notch signaling, instructing ISC self-renewal and lineage decisions. Notably, although a high-fat ketogenic diet elevates ISC function and postinjury regeneration through beta OHB-mediated Notch signaling, a glucose-supplemented diet has the opposite effects. These findings reveal how control of beta OHB-activated signaling in ISCs by diet helps to fine-tune stem cell adaptation in homeostasis and injury.</description>
  </descriptions>
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