Changes of Single Cell Transcriptome And Cellular Composition in Pancreas During Aging

The pancreas is comprised of several distinct populations of cells: exocrine cells (acinar cells) that secrete enzymes into the digestive tract and endocrine cells (alpha-, beta-, gamma- and epsilon-cells) that secrete hormones and ductal cells. Age-related changes in the human pancreas are considered to be the one of the main drivers of pancreatic duodenal adenocarcinoma and diabetes mellitus type 2. However, the mechanisms underlying these transformations are not fully understood. To investigate age-dependent effects in human pancreas we performed single-cell transcriptome analysis of human pancreatic cells from 8 donors of age spanning five decades (GEO ID - GSE81547). The use of single-cell technology has made it possible to reveal age-related effects including changes in the cellular composition of the organ and alterations in the transcriptional landscape within certain cell populations. We obtained an accurate cell type classification based on expression of 43 marker genes. We found a significant increase in the proportion of alpha cells in tissue specimens of aging donors. Transcriptome analysis revealed overexpression of genes coding heat shock proteins and proteins of ubiquitin-dependent proteolytic system in alpha, beta and acinar cells of children, which significantly declines in cells of donors over 20 years old. Age-related increase in the gene expression of transcription factor AP-1 subunits was observed in alpha-cells. A considerable decrease in expression of ribosomal subunits and proteins involved in mitochondrial function was detected in aging beta cells. Likewise, we saw a decline in the gene expression of digestive enzymes in acinar cells. Finally, we developed a new method to perform an analysis of the signaling landscapes in single cells. The designed method revealed the presence of significant changes in the signaling pathway activation in alpha, delta and acinar cells.