Volume 24, Issue 4, Pages (October 2016)

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Volume 24, Issue 4, Pages 608-615 (October 2016) RNA Sequencing of Single Human Islet Cells Reveals Type 2 Diabetes Genes Yurong Xin, Jinrang Kim, Haruka Okamoto, Min Ni, Yi Wei, Christina Adler, Andrew J. Murphy, George D. Yancopoulos, Calvin Lin, Jesper Gromada Cell Metabolism Volume 24, Issue 4, Pages 608-615 (October 2016) DOI: 10.1016/j.cmet.2016.08.018 Copyright © 2016 Elsevier Inc. Terms and Conditions

Cell Metabolism 2016 24, 608-615DOI: (10.1016/j.cmet.2016.08.018) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 1 Distribution of Non-diabetic and T2D Islet Cells (A) Distribution of α, β, δ, and PP cells from 12 non-diabetic and 6 T2D organ donors. (B) Cell-type analysis of 1,492 human islet cells from 12 non-diabetic and 6 T2D organ donors shown with the first two dimensions of t-distributed stochastic neighbor embedding (tSNE) analysis. See also Table S1 and Figures S1–S3. Cell Metabolism 2016 24, 608-615DOI: (10.1016/j.cmet.2016.08.018) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 2 Enriched Genes and Pathways in Non-diabetic and T2D Islet Cells (A) Union of enriched genes in α, β, δ, and PP cells from 12 non-diabetic and 6 T2D organ donors. (B) Pathways and functional gene sets with enriched genes in α, β, δ, and PP cells from 12 non-diabetic and 6 T2D organ donors. (C) Pathways and functional gene sets with abundant genes in α, β, δ, and PP cells from 12 non-diabetic and 6 T2D organ donors. See also Table S2. Cell Metabolism 2016 24, 608-615DOI: (10.1016/j.cmet.2016.08.018) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 3 Differentially Expressed Genes in T2D Islet Cells (A–D) MA plots (fold change to expression level in normalized counts) for genes detected in α cells (n = 54) (A), β cells (n = 48) (B), δ cells (n = 119) (C), and PP cells (n = 33) (D) from 6 T2D and 12 non-diabetic organ donors. Significantly differentially expressed genes in T2D islet cells are highlighted in red. (E) Functions of T2D affected genes in each cell type were characterized as islet growth related, islet functions, non-islet growth related, non-islet functions, and no known functions. See also Figure S4 and Table S3. Cell Metabolism 2016 24, 608-615DOI: (10.1016/j.cmet.2016.08.018) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 4 Correlation of α and β Cell Enriched Gene Expression in Mice and Humans (A) Scatterplot of all homologous genes (black dots) and union of enriched genes (red dots) in α cells from mice and non-diabetic human organ donors. (B) Scatterplot of all homologous genes (black dots) and union of enriched genes (red dots) in β cells from mice and non-diabetic human organ donors. See also Table S4. Cell Metabolism 2016 24, 608-615DOI: (10.1016/j.cmet.2016.08.018) Copyright © 2016 Elsevier Inc. Terms and Conditions