TY - JOUR
T1 - Single-Cell Transcriptomics of the Human Endocrine Pancreas
AU - Wang, Yue J
AU - Schug, Jonathan
AU - Won, Kyoung-Jae
AU - Liu, Chengyang
AU - Naji, Ali
AU - Avrahami, Dana
AU - Golson, Maria L
AU - Kaestner, Klaus H
N1 - © 2016 by the American Diabetes Association.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Human pancreatic islets consist of multiple endocrine cell types. To facilitate the detection of rare cellular states and uncover population heterogeneity, we performed single-cell RNA sequencing (RNA-seq) on islets from multiple deceased organ donors, including children, healthy adults, and individuals with type 1 or type 2 diabetes. We developed a robust computational biology framework for cell type annotation. Using this framework, we show that a- and β-Cells from children exhibit less well-defined gene signatures than those in adults. Remarkably, a- and β-Cells from donors with type 2 diabetes have expression profiles with features seen in children, indicating a partial dedifferentiation process. We also examined a naturally proliferating α-cell from a healthy adult, for which pathway analysis indicated activation of the cell cycle and repression of checkpoint control pathways. Importantly, this replicating α-cell exhibited activated Sonic hedgehog signaling, a pathway not previously known to contribute to human a-cell proliferation. Our study highlights the power of single-cell RNA-seq and provides a stepping stone for future explorations of cellular heterogeneity in pancreatic endocrine cells.
AB - Human pancreatic islets consist of multiple endocrine cell types. To facilitate the detection of rare cellular states and uncover population heterogeneity, we performed single-cell RNA sequencing (RNA-seq) on islets from multiple deceased organ donors, including children, healthy adults, and individuals with type 1 or type 2 diabetes. We developed a robust computational biology framework for cell type annotation. Using this framework, we show that a- and β-Cells from children exhibit less well-defined gene signatures than those in adults. Remarkably, a- and β-Cells from donors with type 2 diabetes have expression profiles with features seen in children, indicating a partial dedifferentiation process. We also examined a naturally proliferating α-cell from a healthy adult, for which pathway analysis indicated activation of the cell cycle and repression of checkpoint control pathways. Importantly, this replicating α-cell exhibited activated Sonic hedgehog signaling, a pathway not previously known to contribute to human a-cell proliferation. Our study highlights the power of single-cell RNA-seq and provides a stepping stone for future explorations of cellular heterogeneity in pancreatic endocrine cells.
KW - Cell Cycle/genetics
KW - Cell Proliferation/genetics
KW - Computational Biology/methods
KW - Diabetes Mellitus, Type 1/genetics
KW - Diabetes Mellitus, Type 2/genetics
KW - Glucagon-Secreting Cells/cytology
KW - Humans
KW - Insulin-Secreting Cells/cytology
KW - Islets of Langerhans/cytology
KW - Microfluidics/methods
KW - Signal Transduction/genetics
KW - Transcriptome/genetics
U2 - 10.2337/db16-0405
DO - 10.2337/db16-0405
M3 - Journal article
C2 - 27364731
SN - 0012-1797
VL - 65
SP - 3028
EP - 3038
JO - Diabetes
JF - Diabetes
IS - 10
ER -
