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.

Dublin Core

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  <dc:creator>Cheng, Chia-Wei</dc:creator>
  <dc:creator>Biton, Moshe</dc:creator>
  <dc:creator>Haber, Adam L.</dc:creator>
  <dc:creator>Gunduz, Nuray</dc:creator>
  <dc:creator>Eng, George</dc:creator>
  <dc:creator>Gaynor, Liam T.</dc:creator>
  <dc:creator>Tripathi, Surya</dc:creator>
  <dc:creator>Calibasi-Koca, Gizem</dc:creator>
  <dc:creator>Rickelt, Steffen</dc:creator>
  <dc:creator>Butty, Vincent L.</dc:creator>
  <dc:creator>Moreno-Serrano, Marta</dc:creator>
  <dc:creator>Iqbal, Ameena M.</dc:creator>
  <dc:creator>Bauer-Rowe, Khristian E.</dc:creator>
  <dc:creator>Imada, Shinya</dc:creator>
  <dc:creator>Ulutas, Mehmet Sefa</dc:creator>
  <dc:creator>Mylonas, Constantine</dc:creator>
  <dc:creator>Whary, Mark T.</dc:creator>
  <dc:creator>Levine, Stuart S.</dc:creator>
  <dc:creator>Basbinar, Yasemin</dc:creator>
  <dc:creator>Hynes, Richard O.</dc:creator>
  <dc:creator>Hynes, Richard O.</dc:creator>
  <dc:date>2019-01-01</dc:date>
  <dc:description>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.</dc:description>
  <dc:identifier>https://aperta.ulakbim.gov.trrecord/72519</dc:identifier>
  <dc:identifier>oai:zenodo.org:72519</dc:identifier>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>http://www.opendefinition.org/licenses/cc-by</dc:rights>
  <dc:source>CELL 178(5) 1115-+</dc:source>
  <dc:title>Ketone Body Signaling Mediates Intestinal Stem Cell Homeostasis and Adaptation to Diet</dc:title>
  <dc:type>info:eu-repo/semantics/article</dc:type>
  <dc:type>publication-article</dc:type>
</oai_dc:dc>