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Multiplex tissue profiling - PancreasThe pancreas panelProtein expression in pancreasProtein expression in alpha cellsProtein expression in beta cellsProtein expression in PP cellsProtein expression in delta cellsProtein expression in epsilon cellsRelevant links and publications
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Pancreas
Tissue methods
Multiplex tissue profiling - PancreasThe pancreas is a composite organ with both exocrine and endocrine functions. The exocrine compartment includes glandular cells that secrete enzymes to the gastrointestinal tract for digestion. The endocrine function of the pancreas is based on the diffusely spread pancreatic endocrine cells, also known as islets of Langerhans. These islets look homogeneous in standard immunohistochemistry (IHC) but consist of multiple cell types secreting different endocrine hormones. As part of the Tissue resource, we used multiplex immunohistochemistry-based fluorescence (mIHC/IF) for in-depth profiling of protein expression in the endocrine pancreas. In the current version, 77 proteins have been analyzed using 1 antibody panel.
The pancreas panelThe mIHC/IF panel for endocrine pancreas was generated to profile the different endocrine cell types in the islets of Langerhans. These islets contain five different cell types; alpha cells, beta cells, PP cells, delta cells and epsilon cells. The mIHC/IF technique is based on the overlap between the location of the candidate protein and location of the marker proteins targeted by the panel antibodies. Figure 1 shows the different cell types/states/structures, and the corresponding marker proteins included in each panel. More information about the multiplex panels can be found here.
Figure 1. A schematic depiction of the pancreas panel on the left with a list of cell types, representing colors and marker proteins on the right. Protein expression in pancreasCandidate proteins for in-depth profiling were selected from the Tissue resource based on cell type specific staining pattern using conventional immunohistochemistry. Multiplex immunohistochemistry has allowed us to analyze and visualize protein expression in pancreas at a higher resolution than ever before. For pancreas, the protein expression was analyzed in alpha cells, beta cells, PP cells, delta cells and epsilon cells.
Protein expression in alpha cellsAlpha cells are the glucagon (GCG) producing cells in the islets of Langerhans, constituting approximately 30% of the cells. As shown in Table 1, 23 genes have main subcellular location in the alpha cells. Some examples of proteins found in alpha cells are the SHC adaptor protein 2 (SHC2) and zinc finger with KRAB and SCAN domains 8 (ZKSCAN8). Another example is VGF nerve growth factor inducible (VGF), which has been described as expressed in a subset of neuroendocrine cells and has been suggested to play many different roles, though currently its exact function is unknown.
Protein expression in beta cellsAround 60% of the islet of Langerhans' cells are insulin (INS) producing beta cells. As shown in Table 1, 41 genes have main subcellular location in the beta cells. A well-known example of a protein found in beta cells is the islet amyloid polypeptide (IAPP), which helps regulate blood glucose levels in response to food intake. Other examples of proteins in the beta cells are the membrane proteins SHISAL2B and DLK1, with limited knowledge on their function.
Protein expression in PP cellsA small fraction (<5%) of the islets of Langerhans is composed of the pancreatic polypeptide Y (PPY) producing PP cells. As shown in Table 1, 19 genes have main subcellular location in the PP cells. Two examples of proteins found in PP cells are the membrane transport proteins solute carrier family 4 member 4 (SLC4A4) which functions as a intracellular pH regulator, and amnion associated transmembrane protein (AMN) with a function in vitamin B12 absorption. Synaptotagmin like 1 (SYTL1) is another example of a protein found in PP cells and is suggested to have a role in vesicle trafficking.
Protein expression in delta cellsLess than 10% of the cells in the islets of Langerhans are somatostatin (SST) expressing delta cells. As shown in Table 1, 7 genes have main subcellular location in the delta cells. KCNJ11 is a potassium channel in which mutations have been associated with increased secretion of insulin. According to our results, it was the only protein exclusively located in delta cells besides SST. Another protein found in delta cells, among other cell types, is syntaxin 1A (STX1A), which plays an important role in endo- and exocytosis. The calcium binding protein reticulocalbin 1 (RCN1) is another example of a protein present in delta cells with a suggested function in the endoplasmic reticulum.
Protein expression in epsilon cellsThe grehlin (GHRL) producing epsilon cells constitute the smallest fraction (<1%) of endocrine cells in the islets of Langerhans. As shown in Table 1, 10 genes have main subcellular location in the epsilon cells. Some examples of proteins detected in the epsilon cells are endoplasmic reticulum to nucleus signaling 1 (ERN1), involved in the endoplasmic reticulum stress response to unfolded proteins, and phospholipid phosphatase 6 (PLPP6), a membrane protein involved in phospholipid dephosphorylation. Secreted phosphoprotein 1 (SPP1) is another example found in epsilon cells with no known function related to endocrine pancreas. SPP1 has been shown to be involved in the interaction of osteoclasts with the mineralized bone matrix.
Relevant links and publications Uhlén M et al., Tissue-based map of the human proteome. Science (2015) |
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