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tisdag 7 maj 2019

Organoidi suolistosoluista

7.5. 2019 haku:  Intestinal stemcell (ISC), Sirtuin

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1.(Tutkimus on tehty  kalan suolesta)
Liu S, Zheng Z, Ji S, Liu T, Hou Y, Li S, Li G.
Fish Shellfish Immunol. 2018 Sep;80:473-479. doi: 10.1016/j.fsi.2018.06.027. Epub 2018 Jun 13.
PMID:
29908321
2.
Ren NSX, Ji M, Tokar EJ, Busch EL, Xu X, Lewis D, Li X, Jin A, Zhang Y, Wu WKK, Huang W, Li L, Fargo DC, Keku TO, Sandler RS, Li X.
Curr Biol. 2017 Feb 20;27(4):483-494. doi: 10.1016/j.cub.2016.12.047. Epub 2017 Feb 2.
3.
Igarashi M, Guarente L.
Cell. 2016 Jul 14;166(2):436-450. doi: 10.1016/j.cell.2016.05.044. Epub 2016 Jun 23.
PMID:
27345368
Highlights
  • Calorie restriction induces mTORC1 and SIRT1 in intestinal stem cells to increase their number
  • The mTORC1 inhibitor rapamycin blocks the effects of calorie restriction on intestinal stem cells
  • Paneth cell signaling increases NAD synthesis in intestinal stem cells during calorie restriction
  • Intestinal stem cells are insulated from directly sensing reduced caloric intake
Free Article
4.
Wakeling LA, Ions LJ, Escolme SM, Cockell SJ, Su T, Dey M, Hampton EV, Jenkins G, Wainwright LJ, McKay JA, Ford D.
Hum Genomics. 2015 Jun 24;9:14. doi: 10.1186/s40246-015-0036-0.
5. Ohutsuoliorganoidi
Cao L, Kuratnik A, Xu W, Gibson JD, Kolling F 4th, Falcone ER, Ammar M, Van Heyst MD, Wright DL, Nelson CE, Giardina C.
Mol Carcinog. 2015 Mar;54(3):189-202. doi: 10.1002/mc.22089. Epub 2013 Sep 21.
Intestinal organoids are multicellular crypt-like structures that can be derived from adult intestinal stem cells (ISCs), embryonic stem cells (ESCs) or induced pluripotent stem cells (IPSCs). Here we show that intestinal organoids generated from mouse ESCs were enriched in ISCs and early progenitors. Treatment of these organoids with a γ-secretase inhibitor increased Math1 and decreased Hes1 expression, indicating Notch signaling regulates ISC differentiation in these organoids. Lgr5 and Tert positive ISCs constituted approximately 10% and 20% of the organoids. As found in native tissue, Lgr5 and Tert expressing cells resolved into two discreet populations, which were stable over time. Intestinal organoids derived from cancer-prone Apc(Min/+) mice showed similar numbers of ISCs, but had reduced Math1 expression, indicating a suppressed secretory cell differentiation potential (as found in intestinal tissue). Apc(Min/+) organoids were used to screen epigenetically active compounds for those that increased Math1 expression and organoid differentiation (including HDAC inhibitors, Sirtuin (SIRT) modulators and methyltransferase inhibitors). Broad-spectrum HDAC inhibitors increased both Math1 and Muc2 expression, indicating an ability to promote the suppressed secretory cell differentiation pathway. Other epigenetic compounds had a diverse impact on cell differentiation, with a strong negative correlation between those that activated the secretory marker Muc2 and those that activated the absorptive cell marker Fabp2. These data show that ESC-derived intestinal organoids can be derived in large numbers, contain distinct ISC types and can be used to screen for agents that promote cell differentiation through different lineage pathways.

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