Pancreatic inactivation of c-Myc decreases acinar mass and transdifferentiates acinar cells into adipocytes in mice
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...
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Published in | Gastroenterology (New York, N.Y. 1943) Vol. 136; no. 1; p. 309 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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United States
01.01.2009
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Abstract | 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.
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.
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.
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. |
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AbstractList | 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.
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.
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.
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. |
Author | Bonal, Claire Trumpp, Andreas Ait-Lounis, Aouatef Herrera, Pedro L Thorel, Fabrizio Reith, Walter |
Author_xml | – sequence: 1 givenname: Claire surname: Bonal fullname: Bonal, Claire organization: Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland – sequence: 2 givenname: Fabrizio surname: Thorel fullname: Thorel, Fabrizio – sequence: 3 givenname: Aouatef surname: Ait-Lounis fullname: Ait-Lounis, Aouatef – sequence: 4 givenname: Walter surname: Reith fullname: Reith, Walter – sequence: 5 givenname: Andreas surname: Trumpp fullname: Trumpp, Andreas – sequence: 6 givenname: Pedro L surname: Herrera fullname: Herrera, Pedro L |
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SubjectTerms | Adipocytes - cytology Animals Cell Differentiation Cell Proliferation Epithelium - pathology Homeodomain Proteins - analysis Humans Mesoderm - pathology Mice Mice, Inbred C57BL Pancreas, Exocrine - pathology Proto-Oncogene Proteins c-myc - analysis Proto-Oncogene Proteins c-myc - physiology Trans-Activators - analysis |
Title | Pancreatic inactivation of c-Myc decreases acinar mass and transdifferentiates acinar cells into adipocytes in mice |
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