DTA

Digital Theses Archive

 

Tesi etd-11112021-215348

Type of thesis
Corsi integrativi
Author
BARBIERO, SILVIA
URN
etd-11112021-215348
Title
The metabolic roots of stemness: lipid storage confers robustness to stem cells potential in intestinal organoids
Structure
Cl. Sc. Sperimentali - Medicina
Course
SCIENZE MEDICHE - SCIENZE MEDICHE
Committee
relatore Prof. EMDIN, MICHELE
Relatore Prof.ssa Prisca Liberali
Membro Prof. COCEANI, FLAVIO
Membro Prof. RECCHIA, FABIO ANASTASIO
Membro Prof. PASSINO, CLAUDIO
Membro Prof. LIONETTI, VINCENZO
Membro Dott. GIANNONI, ALBERTO
Membro Dott.ssa CASIERI, VALENTINA
Membro Prof.ssa ANGELONI, DEBORA
Keywords
  • intestinal organoid regeneration
  • intestinal stem cells
  • lipid metabolism
  • metabolic robustness
Exam session start date
20/12/2021;
Availability
parziale
Abstract
The energetic demands of a cell are mostly met via a dynamic consumption of two main fuels: glucose and fatty acids, which through glycolysis and mitochondrial beta-oxidation respectively ensure fast-but-low or slow-but-high yield of energy production. Although most cells perform both processes, each single cell adopts different metabolic signatures favoring one mode of fuel utilization according to its developmental and functional state. Particularly, the active proliferation accompanying regenerating cell types in most stem cell niches has been linked to increased glycolytic activity, which ensures the fastest replenishment of ATP pool. A shift towards lipid catabolism is then usually observed for cells undergoing differentiation, or for mature cell types. <br>Being directly exposed to the gut lumen and experiencing great daily variability in the blood supply, the intestinal stem cell niche offers a peculiar system to study how stem cells optimize the metabolic balance between glycolysis and beta-oxidation to cope with the unpredictability of their environment. Whilst in homeostasis intestinal stem cells receive metabolic help from crypt-sustaining neighbors in the form of lactate directly fueled in the TCA cycle, they have also been proven to strictly depend on glycolysis for injury-induced regeneration. However, recent findings have shown that in homeostasis increased fatty acid oxidation is sufficient to boost intestinal stem cells’ proliferation and a complex lipid phenotype for intestinal stem cells has just started to be untangled. <br>Here we use mouse intestinal organoids as a highly accessible model to study the reasons and mechanisms underlying the peculiar metabolic lipid signature observed in intestinal stem cells. <br>
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