Multipotent Progenitor Cells in Mouse Fetal Pancreas Are Defined by High Sox9 and Low Ngn3
Daniel F Boyer, Yuping Yang, Christopher VE Wright. Massachusetts General Hospital, Boston; Vanderbilt University School of Medicine, Nashville
Background: There has been considerable controversy regarding the location of multipotent progenitor cells (MPCs) within the developing pancreas and the elucidation of when MPCs become restricted to specific lineages. Neurogenin 3 (Ngn3) has been regarded as an on/off switch for endocrine differentiation; however, lineage-tracing studies in mice show that some Ngn3-expressing cells give rise to ductal and acinar tissue. The transcription factor Sox9 is expressed in fetal pancreatic ducts and is a positive regulator of NGN3. We have studied the location and behavior of cells expressing these factors in order to gain a better understanding of the phenotype of pancreatic MPCs.
Design: Genetic lineage-tracing was performed in transgenic mice expressing Cre recombinase under control of regulatory elements from the NGN3 and SOX9 gene loci. The mice carried a reporter gene allele that produces yellow fluorescent protein (YFP) after Cre-mediated recombination. The lineage-tracing studies were repeated in combination with conditional knock-out of the PDX1 gene, an essential regulator of pancreas development, to assess the function of the putative MPC populations in the developing pancreas.
Results: Ngn3 is expressed in progenitors of pancreatic duct and endocrine tissue. The bipotential duct/endocrine progenitor cells have a characteristic molecular signature of Ngn3lowSox9+Muc1+. The ability of the progenitor cells to give rise to endocrine tissue requires Pdx1, and strong expression of Pdx1 is required for production of beta cells. In the absence of Pdx1, cells specified to endocrine fate undergo apoptosis.
Conclusions: We have identified a proliferative population of bipotential duct/endocrine progenitors that resides in the epithelial layer lining the lumen of the embryonic pancreatic ducts. This progenitor population gives rise to new duct and endocrine cells continuously during embryogenesis, and the ability of these cells to generate endocrine tissue is dependent on Pdx1.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 256, Tuesday Morning