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In the Setting of Beta Cell Stress, the Pancreatic Duct Gland Transcriptome Shows Characteristics of an Activated Regenerative Response.

  • Author(s): Butler, AE
  • Kirakossian, D
  • Gurlo, T
  • Gao, F
  • Coppola, G
  • Butler, PC
  • et al.
Abstract

The pancreatic duct gland (PDG) compartment has been proposed as a potential stem cell niche based on its coiled tubular structure embedded in mesenchyme, its proliferation and expansion in response to pancreatic injury, and the fact that it contains endocrine and exocrine epithelial cells. Little is known of the molecular signature of the PDG compartment in either a quiescent state or the potentially activated state during beta cell stress characteristic of diabetes. To address this, we performed RNA sequencing on RNA obtained from PDGs of wild type versus pre-diabetic HIP rats, a model of type 2 diabetes. The transcriptome of the PDG compartment, compared to a library of 84 tissue types, placed PDGs midpoint between the exocrine and endocrine pancreas and closely related to seminiferous tubules, consistent with a role as a stem cell niche for the exocrine and endocrine pancreas. Standard differential expression analysis (permissive threshold p<0.005) identified 245 genes differentially expressed in PDGs from HIP rats versus WT rats, with overrepresentation of transcripts involved in acute inflammatory responses, regulation of cell proliferation, and tissue development, while pathway analysis pointed to enrichment of cell movement-related pathways. In conclusion the transcriptome of the PDG compartment is consistent with a pancreatic stem cell niche that is activated by ongoing beta cell stress signals. The documented PDG transcriptome provides potential candidates to be exploited for lineage tracing studies of this as yet little investigated compartment.

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