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The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
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After cellular or tissue damage, the resident stem cells present in the human body can locally repair and regenerate the damaged tissue or organ. However, even though some tissues do not have stem cells, they can repair and regenerate with the help of pre-existing cells. For example, beta cells of the pancreas and hepatocytes of the liver can divide to renew and regenerate the tissue. Here, both cell division and cell death are well regulated by homeostasis.
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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Proliferating pancreatic beta-cells upregulate ALDH.

Yinglan Liu1, Xiaoxin Jiang, Yong Zeng

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|July 17, 2014
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Aldehyde dehydrogenase (ALDH) activity, indicated by aldefluor fluorescence, identifies proliferating beta-cells in the pancreas. This finding offers a new method for isolating these cells but suggests aldefluor is unsuitable for tracking stem cells in the adult pancreas.

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Area of Science:

  • Cell Biology
  • Endocrinology
  • Developmental Biology

Background:

  • High aldehyde dehydrogenase (ALDH) activity is a known marker for stem and progenitor cells.
  • Aldehyde dehydrogenase activity has been detected in the embryonic mouse pancreas and specifically in adult centroacinar and terminal duct cells.
  • This suggests these duct cells may possess endocrine and exocrine differentiation potential.

Purpose of the Study:

  • To investigate the presence and characteristics of aldefluor-positive beta-cells in a proliferating beta-cell model.
  • To explore the utility of aldefluor fluorescence as an indicator of beta-cell proliferation.
  • To evaluate the suitability of aldefluor lineage-tracing for stem cell analysis in the adult pancreas.

Main Methods:

  • Utilized a partial pancreatectomy model to induce beta-cell proliferation in mice.
  • Assessed aldefluor fluorescence in beta-cells.
  • Performed immunofluorescence staining for Ki-67, CyclinD1, CyclinD2, and CDK4 to identify mitotic cells.

Main Results:

  • Identified aldefluor-positive beta-cells within the proliferating beta-cell population.
  • Found that aldefluor-positive beta-cells were predominantly Ki-67 positive and expressed high levels of cell-cycle activators.
  • These findings indicate that aldefluor-positive beta-cells are actively mitotic.

Conclusions:

  • Aldehyde dehydrogenase activity is altered in proliferating beta-cells, offering a novel method for their isolation and analysis.
  • Aldehydefluor fluorescence can serve as an indicator of beta-cell proliferation.
  • Aldehydefluor lineage-tracing is not recommended for assessing progenitor or stem cell activity in the adult pancreas.