The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells
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The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells. / Collombat, Patrick; Xu, Xiaobo; Ravassard, Philippe; Sosa-Pineda, Beatriz; Dussaud, Sébastien; Billestrup, Nils; Madsen, Ole D.; Serup, Palle; Heimberg, Harry; Mansouri, Ahmed.
I: Cell, Bind 138, Nr. 3, 2009, s. 449-62.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells
AU - Collombat, Patrick
AU - Xu, Xiaobo
AU - Ravassard, Philippe
AU - Sosa-Pineda, Beatriz
AU - Dussaud, Sébastien
AU - Billestrup, Nils
AU - Madsen, Ole D.
AU - Serup, Palle
AU - Heimberg, Harry
AU - Mansouri, Ahmed
N1 - Keywords: Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation; Diabetes Mellitus, Experimental; Glucagon; Glucagon-Secreting Cells; Homeodomain Proteins; Insulin-Secreting Cells; Islets of Langerhans; Mice; Nerve Tissue Proteins; Paired Box Transcription Factors; Pancreas; Stem Cells
PY - 2009
Y1 - 2009
N2 - We have previously reported that the loss of Arx and/or Pax4 gene activity leads to a shift in the fate of the different endocrine cell subtypes in the mouse pancreas, without affecting the total endocrine cell numbers. Here, we conditionally and ectopically express Pax4 using different cell-specific promoters and demonstrate that Pax4 forces endocrine precursor cells, as well as mature alpha cells, to adopt a beta cell destiny. This results in a glucagon deficiency that provokes a compensatory and continuous glucagon+ cell neogenesis requiring the re-expression of the proendocrine gene Ngn3. However, the newly formed alpha cells fail to correct the hypoglucagonemia since they subsequently acquire a beta cell phenotype upon Pax4 ectopic expression. Notably, this cycle of neogenesis and redifferentiation caused by ectopic expression of Pax4 in alpha cells is capable of restoring a functional beta cell mass and curing diabetes in animals that have been chemically depleted of beta cells.
AB - We have previously reported that the loss of Arx and/or Pax4 gene activity leads to a shift in the fate of the different endocrine cell subtypes in the mouse pancreas, without affecting the total endocrine cell numbers. Here, we conditionally and ectopically express Pax4 using different cell-specific promoters and demonstrate that Pax4 forces endocrine precursor cells, as well as mature alpha cells, to adopt a beta cell destiny. This results in a glucagon deficiency that provokes a compensatory and continuous glucagon+ cell neogenesis requiring the re-expression of the proendocrine gene Ngn3. However, the newly formed alpha cells fail to correct the hypoglucagonemia since they subsequently acquire a beta cell phenotype upon Pax4 ectopic expression. Notably, this cycle of neogenesis and redifferentiation caused by ectopic expression of Pax4 in alpha cells is capable of restoring a functional beta cell mass and curing diabetes in animals that have been chemically depleted of beta cells.
U2 - 10.1016/j.cell.2009.05.035
DO - 10.1016/j.cell.2009.05.035
M3 - Journal article
C2 - 19665969
VL - 138
SP - 449
EP - 462
JO - Cell
JF - Cell
SN - 0092-8674
IS - 3
ER -
ID: 18698190