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Pancreatic inactivation of c-Myc decreases acinar mass and transdifferentiates acinar cells into adipocytes in mice

Bonal, Claire
Ait-Lounis, Aouatef
Trumpp, Andreas
Published in Gastroenterology. 2009, vol. 136, no. 1, p. 309-319 e309
Abstract BACKGROUND & AIMS: The pancreatic mass is determined by the coordinated expansion and differentiation of progenitor cells and is maintained via tight control of cell replacement rates. The basic helix-loop-helix transcription factor c-Myc is one of the main regulators of these processes in many organs. We studied the requirement of c-Myc in controlling the generation and maintenance of pancreatic mass. METHODS: We conditionally inactivated c-Myc in Pdx1+ pancreatic progenitor cells. Pancreata of mice lacking c-Myc (c-Myc(P-/-) mice) were analyzed during development and ageing. RESULTS: Pancreatic growth in c-Myc(P-/-) mice was impaired starting on E12.5, in early primordia, because of decreased proliferation and altered differentiation of exocrine progenitors; islet progenitors were spared. Acinar cell maturation was defective in the adult hypotrophic pancreas, which hampered exocrine mass maintenance in aged animals. From 2 to 10 months of age, the c-Myc(P-/-) pancreas was progressively remodeled without inflammatory injury. Loss of acinar cells increased with time, concomitantly with adipose tissue accumulation. Using a genetic cell lineage tracing analysis, we demonstrated that pancreatic adipose cells were derived directly from transdifferentiating acinar cells. This epithelial-to-mesenchyme transition was also observed in normal aged specimens and in pancreatitis. CONCLUSIONS: These results provide evidence indicating that c-Myc activity is required for growth and maturation of the exocrine pancreas, and sheds new light on the ontogeny of pancreatic adipose cells in processes of organ degenerescence and tissue involution.
Keywords Adipocytes/ cytologyAnimalsCell DifferentiationCell ProliferationEpithelium/pathologyHomeodomain Proteins/analysisHumansMesoderm/pathologyMiceMice, Inbred C57BLPancreas, Exocrine/ pathologyProto-Oncogene Proteins c-myc/analysis/ physiologyTrans-Activators/analysis
PMID: 19022256
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Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
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BONAL, Claire et al. Pancreatic inactivation of c-Myc decreases acinar mass and transdifferentiates acinar cells into adipocytes in mice. In: Gastroenterology, 2009, vol. 136, n° 1, p. 309-319 e309. doi: 10.1053/j.gastro.2008.10.015 https://archive-ouverte.unige.ch/unige:8650

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Deposited on : 2010-07-12

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