Single-Cell Transcriptomics of the Human Endocrine Pancreas

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 -