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. Author manuscript; available in PMC: 2020 Mar 5.
Published in final edited form as: Cell Metab. 2019 Jan 31;29(3):769–783.e4. doi: 10.1016/j.cmet.2019.01.003

Figure 4.

Figure 4.

Quantification of protein expressions at the cellular level in the human pancreas. See also Figure S6.

(A) Heatmap demonstrates that endocrine cells from different donors cluster by their cell types and display canonical marker expression. Input data are mean levels of each protein in each cell type for each donor type. Values associated with each row of the heatmap are centered and standardized separately. Heatmap color indicates Z-score.

(B) Violin plots summarize the relative expressions of C-PEP (left panel), PDX1 (middle panel), and NKX6.1 (right panel) in the beta cells from different donors. Measurements from individual beta cell are used as input. Dot inside each violin represents the location of the population median for Ctrl, T1D≤2, T1D≤11 groups and the expression of the one beta cell in the T1D≥21 group. Red outlines indicate statistical significance, tested by linear mixed effects model with individual protein expression as response and donor types as predictor. Individual donor effect is adjusted as random effect, and p ≤ 0.05 is set as significant cutoff.

(C) Scatter plots display PDX1 versus NKX6.1 expression for all pancreatic endocrine and ductal cells. Each dot represents one cell. The same scatter plot is color coded by donor types (left panel), NF-Κb expression (middle-left panel), C-PEP expression (middle-right panel), and GCG expression (right panel). Four populations emerge based on different levels of PDX1 and NKX6.1 expression. Left panel, group 2 is enriched for cells from control donors (coral dots); while group 3 is enriched for cells from T1D donors (green, turquoise, and violet dots for cells from T1D≤2, T1D≤11 and T1D≥21 groups correspondingly). Middle-left panel, ductal cells are located in group 1, and are characterized by high NF-κB expression. Middle-right panel, beta cells are located in group 2 and have high C-PEP level. Right panel, group 3 cells have high GCG level, indicating their alpha-cell identity. Some of the alpha cells (identified by high GCG expression) also extend into Group 4 regions.

(D) IMC data confirms the ectopic expression of NKX6.1 in alpha cells from T1D donors. Displayed channels are: GCG (green); NKX6.1 (red); C-PEP and SST (blue); PDX1 (white). The levels of NKX6.1 and PDX1 are separately adjusted for visualization in the control panel, due to the significant higher signals of these two channels in the islets from control donors. All panels are shown at 4× magnification.