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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{
  "DOI": "10.1016/j.cell.2019.07.048", 
  "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.", 
  "author": [
    {
      "family": "Cheng", 
      "given": " Chia-Wei"
    }, 
    {
      "family": "Biton", 
      "given": " Moshe"
    }, 
    {
      "family": "Haber", 
      "given": " Adam L."
    }, 
    {
      "family": "Gunduz", 
      "given": " Nuray"
    }, 
    {
      "family": "Eng", 
      "given": " George"
    }, 
    {
      "family": "Gaynor", 
      "given": " Liam T."
    }, 
    {
      "family": "Tripathi", 
      "given": " Surya"
    }, 
    {
      "family": "Calibasi-Koca", 
      "given": " Gizem"
    }, 
    {
      "family": "Rickelt", 
      "given": " Steffen"
    }, 
    {
      "family": "Butty", 
      "given": " Vincent L."
    }, 
    {
      "family": "Moreno-Serrano", 
      "given": " Marta"
    }, 
    {
      "family": "Iqbal", 
      "given": " Ameena M."
    }, 
    {
      "family": "Bauer-Rowe", 
      "given": " Khristian E."
    }, 
    {
      "family": "Imada", 
      "given": " Shinya"
    }, 
    {
      "family": "Ulutas", 
      "given": " Mehmet Sefa"
    }, 
    {
      "family": "Mylonas", 
      "given": " Constantine"
    }, 
    {
      "family": "Whary", 
      "given": " Mark T."
    }, 
    {
      "family": "Levine", 
      "given": " Stuart S."
    }, 
    {
      "family": "Basbinar", 
      "given": " Yasemin"
    }, 
    {
      "family": "Hynes", 
      "given": " Richard O."
    }, 
    {
      "family": "Hynes", 
      "given": " Richard O."
    }
  ], 
  "container_title": "CELL", 
  "id": "72519", 
  "issue": "5", 
  "issued": {
    "date-parts": [
      [
        2019, 
        1, 
        1
      ]
    ]
  }, 
  "page": "1115-+", 
  "title": "Ketone Body Signaling Mediates Intestinal Stem Cell Homeostasis and Adaptation to Diet", 
  "type": "article-journal", 
  "volume": "178"
}