Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes

doi:10.1016/j.cmet.2016.08.020

PMID: 27667667DOI: 10.1016/j.cmet.2016.08.020Sep 27, 2016

Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes

Cell Metabolism

Åsa SegerstolpeRickard Sandberg

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Abstract

Hormone-secreting cells within pancreatic islets of Langerhans play important roles in metabolic homeostasis and disease. However, their transcriptional characterization is still incomplete. Here, we sequenced the transcriptomes of thousands of human islet cells from healthy and type 2 diabetic donors. We could define specific genetic programs for each individual endocrine and exocrine cell type, even for rare δ, γ, ε, and stellate cells, and revealed subpopulations of α, β, and acinar cells. Intriguingly, δ cells expressed several important receptors, indicating an unrecognized importance of these cells in integrating paracrine and systemic metabolic signals. Genes previously associated with obesity or diabetes were found to correlate with BMI. Finally, comparing healthy and T2D transcriptomes in a cell-type resolved manner uncovered candidates for future functional studies. Altogether, our analyses demonstrate the utility of the generated single-cell gene expression resource.

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Apr 26, 2020·Diabetes·Rosemary LiRupangi C Vasavada

Deep learning enables accurate clustering with batch effect removal in single-cell RNA-seq analysis

May 13, 2020·Nature Communications·Xiangjie LiMingyao Li

Flexible experimental designs for valid single-cell RNA-sequencing experiments allowing batch effects correction

Jul 3, 2020·Nature Communications·Fangda SongYingying Wei

Integrating the inputs that shape pancreatic islet hormone release

Jul 23, 2020·Nature Metabolism·Glyn M Noguchi, Mark O Huising

The Connexin 43 Regulator Rotigaptide Reduces Cytokine-Induced Cell Death in Human Islets

Jun 21, 2020·International Journal of Molecular Sciences·Seyed M GhiasiThomas Mandrup-Poulsen

Quantile normalization of single-cell RNA-seq read counts without unique molecular identifiers

Jul 6, 2020·Genome Biology·F William Townes, Rafael A Irizarry

Integrating Deep Supervised, Self-Supervised and Unsupervised Learning for Single-Cell RNA-seq Clustering and Annotation

Jul 18, 2020·Genes·Liang ChenMinghua Deng

Deep learning-based cell composition analysis from tissue expression profiles

Aug 25, 2020·Science Advances·Kevin MendenStefan Bonn

Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D

Oct 2, 2020·Nature Communications·Ana ViñuelaMark I McCarthy

Pancreatic Islet Protein Complexes and Their Dysregulation in Type 2 Diabetes

May 6, 2017·Frontiers in Genetics·Helle Krogh PedersenSøren Brunak

Transcriptome analysis of pancreatic cells across distant species highlights novel important regulator genes

Mar 23, 2017·BMC Biology·Estefania Tarifeño-SaldiviaBernard Peers

scmap: projection of single-cell RNA-seq data across data sets

Apr 3, 2018·Nature Methods·Vladimir Yu KiselevMartin Hemberg

Single-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV

Sep 21, 2018·JCI Insight·Shelli F FarhadianSerena S Spudich

Secretagogin is increased in plasma from type 2 diabetes patients and potentially reflects stress and islet dysfunction

Apr 28, 2018·PloS One·Sara F HanssonPia Davidsson

Machine learning based classification of cells into chronological stages using single-cell transcriptomics

Nov 23, 2018·Scientific Reports·Sumeet Pal SinghJohn E Reid

Endocrine cell type sorting and mature architecture in the islets of Langerhans require expression of Roundabout receptors in β cells

Jul 20, 2018·Scientific Reports·Melissa T AdamsBarak Blum

Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations

Oct 24, 2018·Nature Communications·Sonya A MacParlandIan D McGilvray

Highly specific monoclonal antibodies for allosteric inhibition and immunodetection of the human pancreatic zinc transporter ZnT8

Sep 6, 2018·The Journal of Biological Chemistry·Chengfeng MerrimanDax Fu

Melatonin in type 2 diabetes mellitus and obesity

Dec 12, 2018·Nature Reviews. Endocrinology·Angeliki Karamitri, Ralf Jockers

Single cell RNA-seq data clustering using TF-IDF based methods

Oct 28, 2018·BMC Genomics·Marmar Moussa, Ion I Măndoiu

Genetic, Functional, and Immunological Study of ZnT8 in Diabetes

Apr 3, 2019·International Journal of Endocrinology·Qiong HuangZhicheng Gong

Glucose and amino acid metabolism in mice depend mutually on glucagon and insulin receptor signaling

Feb 27, 2019·American Journal of Physiology. Endocrinology and Metabolism·Katrine D GalsgaardJens J Holst

Evaluating measures of association for single-cell transcriptomics

Apr 10, 2019·Nature Methods·Michael A SkinniderLeonard J Foster

NIH Initiative to Improve Understanding of the Pancreas, Islet, and Autoimmunity in Type 1 Diabetes: The Human Pancreas Analysis Program (HPAP)

May 28, 2019·Diabetes·Klaus H KaestnerMark A Atkinson

Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma

Jul 6, 2019·Cell Research·Junya PengWenming Wu

Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes

Aug 12, 2019·Current Diabetes Reports·Abu Saleh Md Moin, Alexandra E Butler

Localization of Glucagon-Like Peptide-2 Receptor Expression in the Mouse

Jun 27, 2019·Endocrinology·Bernardo YustaDaniel J Drucker

Incretins in obesity and diabetes

Aug 9, 2019·Annals of the New York Academy of Sciences·Chee W Chia, Josephine M Egan

Differential impact of the ERBB receptors EGFR and ERBB2 on the initiation of precursor lesions of pancreatic ductal adenocarcinoma

Apr 7, 2020·Scientific Reports·Nora MeyersPatrick Jacquemin

Gene-edited human stem cell-derived β cells from a patient with monogenic diabetes reverse preexisting diabetes in mice

Apr 24, 2020·Science Translational Medicine·Kristina G MaxwellJeffrey R Millman

scDC: single cell differential composition analysis

Dec 25, 2019·BMC Bioinformatics·Yue CaoKitty K Lo

AAV8 Ins1-Cre can produce efficient β-cell recombination but requires consideration of off-target effects

Jul 1, 2020·Scientific Reports·Adam RamzyTimothy J Kieffer

Pancreatic and intestinal endocrine cells in zebrafish share common transcriptomic signatures and regulatory programmes

Sep 2, 2020·BMC Biology·Arnaud LavergneBernard Peers

Leader β-cells coordinate Ca2+ dynamics across pancreatic islets in vivo

Jul 23, 2020·Nature Metabolism·Victoria SalemGuy A Rutter

Putative cell type discovery from single-cell gene expression data

May 20, 2020·Nature Methods·Zhichao MiaoSarah A Teichmann

EnClaSC: a novel ensemble approach for accurate and robust cell-type classification of single-cell transcriptomes

Sep 18, 2020·BMC Bioinformatics·Xiaoyang ChenRui Jiang

A cullin 4B-RING E3 ligase complex fine-tunes pancreatic δ cell paracrine interactions

Jun 13, 2017·The Journal of Clinical Investigation·Qing LiXiao Yu

Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes

Dec 1, 2017·Diabetologia·Michele SolimenaPiero Marchetti

The case for too little melatonin signalling in increased diabetes risk

Mar 21, 2017·Diabetologia·Amélie Bonnefond, Philippe Froguel

GLP-1 suppresses glucagon secretion in human pancreatic alpha-cells by inhibition of P/Q-type Ca2+ channels

Sep 7, 2018·Physiological Reports·Reshma RamracheyaLinford J B Briant

Assessing the reliability of spike-in normalization for analyses of single-cell RNA sequencing data

Oct 17, 2017·Genome Research·Aaron T L LunJohn C Marioni

Approaches and advances in the genetic causes of autoimmune disease and their implications

Jun 22, 2018·Nature Immunology·Jamie R J InshawJohn A Todd

The Impact of Pancreatic Beta Cell Heterogeneity on Type 1 Diabetes Pathogenesis

Sep 26, 2018·Current Diabetes Reports·Richard K P BenningerGuy A Rutter

Bioinspired, nanoscale approaches in contemporary bioanalytics (Review)

Jul 28, 2018·Biointerphases·H Michelle GrandinFredrik Höök

Ablation of somatostatin cells leads to impaired pancreatic islet function and neonatal death in rodents

Jun 9, 2018·Cell Death & Disease·Na LiXiao Yu

Physiology and Pharmacology of DPP-4 in Glucose Homeostasis and the Treatment of Type 2 Diabetes

Mar 5, 2019·Frontiers in Endocrinology·Carolyn F Deacon

Bulk tissue cell type deconvolution with multi-subject single-cell expression reference

Jan 24, 2019·Nature Communications·Xuran WangMingyao Li

Role of innate immune cells in metabolism: from physiology to type 2 diabetes

Apr 7, 2019·Seminars in Immunopathology·Elise Dalmas

Inferring population dynamics from single-cell RNA-sequencing time series data

Apr 3, 2019·Nature Biotechnology·David S FischerFabian J Theis

Endogenous Pancreatic β Cell Regeneration: A Potential Strategy for the Recovery of β Cell Deficiency in Diabetes

Mar 8, 2019·Frontiers in Endocrinology·Fan Zhong, Yan Jiang

Fast, sensitive and accurate integration of single-cell data with Harmony

Nov 20, 2019·Nature Methods·Ilya KorsunskySoumya Raychaudhuri

A microRNA‑24‑to‑secretagogin regulatory pathway mediates cholesterol‑induced inhibition of insulin secretion

Jun 8, 2019·International Journal of Molecular Medicine·Jing YangJianghua Liu

No direct effect of SGLT2 activity on glucagon secretion

Mar 25, 2019·Diabetologia·Rune E KuhreJens J Holst

Down-regulation of the islet-specific zinc transporter-8 (ZnT8) protects human insulinoma cells against inflammatory stress

Oct 9, 2019·The Journal of Biological Chemistry·Chengfeng Merriman, Dax Fu

Current best practices in single-cell RNA-seq analysis: a tutorial

Jun 21, 2019·Molecular Systems Biology·Malte D Luecken, Fabian J Theis

scAlign: a tool for alignment, integration, and rare cell identification from scRNA-seq data

Aug 16, 2019·Genome Biology·Nelson Johansen, Gerald Quon

Life-long impairment of glucose homeostasis upon prenatal exposure to psychostimulants

Nov 22, 2019·The EMBO Journal·Solomiia KorchynskaTibor Harkany

SCDC: bulk gene expression deconvolution by multiple single-cell RNA sequencing references

Jan 12, 2020·Briefings in Bioinformatics·Meichen DongYuchao Jiang

Tamarind Trypsin Inhibitor in Chitosan-Whey Protein Nanoparticles Reduces Fasting Blood Glucose Levels without Compromising Insulinemia: A Preclinical Study

Nov 20, 2019·Nutrients·Lídia L R MatiasAna H A Morais

Noninvasive Evaluation of GPR119 Agonist Effects on β-Cell Mass in Diabetic Male Mice Using 111In-Exendin-4 SPECT/CT

Oct 16, 2019·Endocrinology·Takaaki MurakamiNobuya Inagaki

Glucose, adrenaline and palmitate antagonistically regulate insulin and glucagon secretion in human pseudoislets

Jul 18, 2019·Scientific Reports·Estela Lorza-GilSusanne Ullrich

Single-cell resolution analysis of the human pancreatic ductal progenitor cell niche

May 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·Mirza Muhammad Fahd QadirJuan Domínguez-Bendala

VEGF-B ablation in pancreatic β-cells upregulates insulin expression without affecting glucose homeostasis or islet lipid uptake

Jan 24, 2020·Scientific Reports·Frank Chenfei NingDaniel Nyqvist

Secretin release after Roux-en-Y gastric bypass reveals a population of glucose-sensitive S cells in distal small intestine

Feb 5, 2020·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Ida M ModvigJens J Holst

Mechanisms of Macrophage Polarization in Insulin Signaling and Sensitivity

Mar 7, 2020·Frontiers in Endocrinology·Lucie OrliaguetFawaz Alzaid

clustifyr: an R package for automated single-cell RNA sequencing cluster classification

Aug 9, 2020·F1000Research·Rui FuKent A Riemondy

Serum biomarkers from cell-based assays for AhRL and MIS strongly predicted the future development of diabetes in a large community-based prospective study in Korea

Apr 15, 2020·Scientific Reports·Hong Kyu LeeYoungmi Kim Pak

Single-cell RNA-seq with spike-in cells enables accurate quantification of cell-specific drug effects in pancreatic islets

May 8, 2020·Genome Biology·Brenda Marquina-SanchezStefan Kubicek

MiRNAs in β-Cell Development, Identity, and Disease

Jan 27, 2017·Frontiers in Genetics·Aida Martinez-SanchezMathieu Latreille

Pancreatic Beta Cell Identity in Humans and the Role of Type 2 Diabetes

Jun 8, 2017·Frontiers in Cell and Developmental Biology·Piero MarchettiLorella Marselli

Single-cell transcriptomics of East-Asian pancreatic islets cells

Jul 12, 2017·Scientific Reports·Rajkumar DorajooBernhard O Boehm

New Understanding of β-Cell Heterogeneity and In Situ Islet Function

Mar 22, 2018·Diabetes·Richard K P Benninger, David J Hodson

Epigenetic Control of Endocrine Pancreas Differentiation in vitro : Current Knowledge and Future Perspectives

Nov 10, 2018·Frontiers in Cell and Developmental Biology·Veronica Astro, Antonio Adamo

Gene expression profiling of periodontitis-affected gingival tissue by spatial transcriptomics

Jun 21, 2018·Scientific Reports·Anna LundmarkTülay Yucel-Lindberg

CellBIC: bimodality-based top-down clustering of single-cell RNA sequencing data reveals hierarchical structure of the cell type

Aug 14, 2018·Nucleic Acids Research·Junil KimKyoung Jae Won

β-Cell Fate in Human Insulin Resistance and Type 2 Diabetes: A Perspective on Islet Plasticity

May 22, 2019·Diabetes·Teresa MezzaAndrea Giaccari

scds: computational annotation of doublets in single-cell RNA sequencing data

Sep 11, 2019·Bioinformatics·Abha S Bais, Dennis Kostka

Gestational Diabetes Adversely Affects Pancreatic Islet Architecture and Function in the Male Rat Offspring

Jun 27, 2019·Endocrinology·Prasoon AgarwalVernon W Dolinsky

Discordance between GLP-1R gene and protein expression in mouse pancreatic islet cells

Jun 20, 2020·The Journal of Biological Chemistry·Sarah M GrayDavid A D'Alessio

A benchmark of batch-effect correction methods for single-cell RNA sequencing data

Jan 18, 2020·Genome Biology·Hoa Thi Nhu TranJinmiao Chen

A Pilot Screen of a Novel Peptide Hormone Library Identified Candidate GPR83 Ligands

Jul 28, 2020·SLAS Discovery·Nathan A SalleeKathleen M C Sullivan

Advances Toward Engineering Functionally Mature Human Pluripotent Stem Cell-Derived β Cells

Aug 1, 2020·Frontiers in Bioengineering and Biotechnology·Leonardo Velazco-CruzJeffrey R Millman

The magnesium transporter NIPAL1 is a pancreatic islet-expressed protein that conditionally impacts insulin secretion

May 23, 2020·The Journal of Biological Chemistry·Yousef ManialawyMichael B Wheeler

Age-dependent human β cell proliferation induced by glucagon-like peptide 1 and calcineurin signaling

Sep 19, 2017·The Journal of Clinical Investigation·Chunhua DaiAlvin C Powers

The Importance of REST for Development and Function of Beta Cells

Mar 14, 2017·Frontiers in Cell and Developmental Biology·David Martin, Anne Grapin-Botton

MANF protects human pancreatic beta cells against stress-induced cell death

Jul 23, 2018·Diabetologia·Elina HakonenTimo Otonkoski

The α-cell in diabetes mellitus

Oct 13, 2018·Nature Reviews. Endocrinology·Jesper GromadaGuy A Rutter

Predictability of human differential gene expression

Mar 9, 2019·Proceedings of the National Academy of Sciences of the United States of America·Megan CrowJesse Gillis

Islet inflammation in type 2 diabetes

Apr 17, 2019·Seminars in Immunopathology·Marianne Böni-Schnetzler, Daniel T Meier

Multivalent activation of GLP-1 and sulfonylurea receptors modulates β-cell second-messenger signaling and insulin secretion

Nov 9, 2018·American Journal of Physiology. Cell Physiology·Nathaniel J HartRonald M Lynch

Targeted delivery of antisense oligonucleotides to pancreatic β-cells

Oct 23, 2018·Science Advances·C ÄmmäläS Andersson

scMerge leverages factor analysis, stable expression, and pseudoreplication to merge multiple single-cell RNA-seq datasets

Apr 28, 2019·Proceedings of the National Academy of Sciences of the United States of America·Yingxin LinJean Yee Hwa Yang

PYY, a Therapeutic Option for Type 2 Diabetes?

Feb 8, 2020·Clinical Medicine Insights. Endocrinology and Diabetes·Claudia Guida, Reshma Ramracheya

Single-cell transcriptomic analysis reveals dynamic alternative splicing and gene regulatory networks among pancreatic islets

Jun 24, 2020·Science China. Life Sciences·Yunjin LiGeng Chen

Loss of the transcription factor MAFB limits β-cell derivation from human PSCs

Jun 4, 2020·Nature Communications·Ronan RussellMatthias Hebrok

Glucose transporters in pancreatic islets

May 13, 2020·Pflügers Archiv : European journal of physiology·Constantin Berger, Daniela Zdzieblo

A call for improved reporting of human islet characteristics in research articles

Dec 14, 2018·Diabetologia·Vincent PoitoutSally M Marshall

β-Cells are not uniform after all-Novel insights into molecular heterogeneity of insulin-secreting cells

Sep 8, 2017·Diabetes, Obesity & Metabolism·Dana AvrahamiKlaus H Kaestner

Use of human islets to understand islet biology and diabetes: progress, challenges and suggestions

Dec 14, 2018·Diabetologia·Nathaniel J Hart, Alvin C Powers

BERMUDA: a novel deep transfer learning method for single-cell RNA sequencing batch correction reveals hidden high-resolution cellular subtypes

Aug 14, 2019·Genome Biology·Tongxin WangKun Huang

Identification of cell types from single cell data using stable clustering

Jul 25, 2020·Scientific Reports·Azam PeyvandipourSorin Draghici

FFA2-, but not FFA3-agonists inhibit GSIS of human pseudoislets: a comparative study with mouse islets and rat INS-1E cells

Oct 7, 2020·Scientific Reports·Estela Lorza-GilSusanne Ullrich

A review of computational strategies for denoising and imputation of single-cell transcriptomic data

Oct 2, 2020·Briefings in Bioinformatics·Lucrezia PatrunoAlex Graudenzi

Optimized design of single-cell RNA sequencing experiments for cell-type-specific eQTL analysis

Nov 1, 2020·Nature Communications·Igor MandricEran Halperin

Glucagon-Like Peptide-1 (GLP-1) in the Integration of Neural and Endocrine Responses to Stress

Nov 1, 2020·Nutrients·Yolanda Diz-ChavesFederico Mallo

Benchmarking of cell type deconvolution pipelines for transcriptomics data

Nov 8, 2020·Nature Communications·Francisco Avila CobosKatleen De Preter

Inhibitory effect of UDP-glucose on cAMP generation and insulin secretion

Aug 29, 2020·The Journal of Biological Chemistry·Fariborz ParandehAlbert Salehi

α2 -Adrenergic Disruption of β Cell BDNF-TrkB Receptor Tyrosine Kinase Signaling

Nov 13, 2020·Frontiers in Cell and Developmental Biology·Michael A KalwatMelanie H Cobb

CSEA-DB: an omnibus for human complex trait and cell type associations

Nov 20, 2020·Nucleic Acids Research·Yulin DaiZhongming Zhao

gCAnno: a graph-based single cell type annotation method

Nov 25, 2020·BMC Genomics·Xiaofei YangKai Ye

Single-cell lineage analysis reveals extensive multimodal transcriptional control during directed beta-cell differentiation

Dec 2, 2020·Nature Metabolism·Chen WengYan Li

Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study

Dec 3, 2020·Genome Medicine·Valborg GudmundsdottirSøren Brunak

Epigenetic landscape of pancreatic neuroendocrine tumours reveals distinct cells of origin and means of tumour progression

Dec 9, 2020·Communications Biology·Annunziata Di DomenicoIlaria Marinoni

Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts

Jun 15, 2019·Cancer Discovery·Ela ElyadaDavid A Tuveson

Single-Cell Transcriptomics of Pancreatic Cancer Precursors Demonstrates Epithelial and Microenvironmental Heterogeneity as an Early Event in Neoplastic Progression

Nov 3, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Vincent BernardHector A Alvarez

Maternally expressed gene 3 in metabolic programming

Jul 5, 2019·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Samuel HamiltonMichel Bernier

"Omics" and "epi-omics" underlying the β-cell adaptation to insulin resistance

Sep 11, 2019·Molecular Metabolism·Dario F De Jesus, Rohit N Kulkarni

Single-Nucleus and In Situ RNA-Sequencing Studies Reveal Cell Topographies in the Human Pancreas

Nov 20, 2020·Gastroenterology·Luca TostiChristian Conrad

Heterogeneity of human pancreatic β-cells

Sep 11, 2019·Molecular Metabolism·Giselle Dominguez-GutierrezJesper Gromada

The dynamic methylome of islets in health and disease

Sep 11, 2019·Molecular Metabolism·Dana Avrahami, Klaus H Kaestner

Informing β-cell regeneration strategies using studies of heterogeneity

Sep 11, 2019·Molecular Metabolism·Daniela NasteskaDavid J Hodson

PANCREATIC BETA CELLS COMMUNICATE WITH VAGAL SENSORY NEURONS

Oct 31, 2020·Gastroenterology·Madina MakhmutovaAlejandro Caicedo

Related Concepts

GLP1R protein, human

Glucagon-Like Peptide-1 Receptor

Diabetes Mellitus, Non-Insulin-Dependent

Islets of Langerhans

Obesity

Tissue Donors

Transcription Factor

Reproducibility of Results

MRNA Differential Display

Single-Cell Analysis

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