Statistical approaches and software for clustering islet cell functional heterogeneity.

Abstract:

:Worldwide efforts are underway to replace or repair lost or dysfunctional pancreatic β-cells to cure diabetes. However, it is unclear what the final product of these efforts should be, as β-cells are thought to be heterogeneous. To enable the analysis of β-cell heterogeneity in an unbiased and quantitative way, we developed model-free and model-based statistical clustering approaches, and created new software called TraceCluster. Using an example data set, we illustrate the utility of these approaches by clustering dynamic intracellular Ca(2+) responses to high glucose in ∼300 simultaneously imaged single islet cells. Using feature extraction from the Ca(2+) traces on this reference data set, we identified 2 distinct populations of cells with β-like responses to glucose. To the best of our knowledge, this report represents the first unbiased cluster-based analysis of human β-cell functional heterogeneity of simultaneous recordings. We hope that the approaches and tools described here will be helpful for those studying heterogeneity in primary islet cells, as well as excitable cells derived from embryonic stem cells or induced pluripotent cells.

journal_name

Islets

journal_title

Islets

authors

Wills QF,Boothe T,Asadi A,Ao Z,Warnock GL,Kieffer TJ,Johnson JD

doi

10.1080/19382014.2016.1150664

subject

Has Abstract

pub_date

2016-03-03 00:00:00

pages

48-56

issue

2

eissn

1938-2014

issn

1938-2022

journal_volume

8

pub_type

杂志文章

相关文献

Islets文献大全
  • Long-term function and optimization of mouse and human islet transplantation in the subcutaneous device-less site.

    abstract::Clinical islet transplantation has routinely been demonstrated to be an efficacious means of restoring glycemic control in select patients with autoimmune diabetes. Notwithstanding marked progress and improvements, the broad-spectrum application of this treatment option is restricted by the complications associated wi...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.1080/19382014.2016.1253652

    authors: Pepper AR,Bruni A,Pawlick RL,Gala-Lopez B,Rafiei Y,Wink J,Kin T,Shapiro AM

    更新日期:2016-11-01 00:00:00

  • Islet amyloidosis in a child with type 1 diabetes.

    abstract::Histopathology based studies of the pancreas obtained from organ donors are increasing our awareness of islet phenotypic heterogeneity during development and aging, as well as in settings of type 1 diabetes, type 2 diabetes, monogenic diabetes or other forms of this metabolic disease. Islet amyloidosis represents a hi...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.1080/19382014.2019.1599707

    authors: Beery ML,Jacobsen LM,Atkinson MA,Butler AE,Campbell-Thompson M

    更新日期:2019-01-01 00:00:00

  • Overexpression of PAX4 reduces glucagon expression in differentiating hESCs.

    abstract::Human embryonic stem cells (hESCs) are pluripotent and capable of generating new β-cells, but current in vitro differentiation protocols generally fail to produce mature, glucose-responsive, unihormonal β-cells. Instead, these methods tend to produce immature polyhormonal endocrine cells which mature in vivo into gluc...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.29236

    authors: Gage BK,Baker RK,Kieffer TJ

    更新日期:2014-01-01 00:00:00

  • The multiple alternatives of intracellular calcium signaling: a functionally distinct RyR splicing variant in pancreatic islets.

    abstract::The sophistication of intracellular Ca ( 2+) signalling reflects the necessity for the many different types of cells to fine tuning their specific activities. This can, at least in part, be explained by the molecular complexity of the Ca ( 2+) signalling machinery, consisting of different intracellular Ca ( 2+) releas...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.2.6.13859

    authors: Rossi D,Sorrentino V

    更新日期:2010-11-01 00:00:00

  • Downregulation of ZnT8 expression in pancreatic β-cells of diabetic mice.

    abstract::Zinc transporter 8 (ZnT8) has been identified as a β-cell-specific Zinc transporter expressed in insulin-secretory granules. Recent genome wide association studies indicated that Arg325Trp polymorphism of Slc30a8 encoding ZnT8 is associated with susceptibility to type 2 diabetes. As a first step towards understanding ...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.1.2.9433

    authors: Tamaki M,Fujitani Y,Uchida T,Hirose T,Kawamori R,Watada H

    更新日期:2009-09-01 00:00:00

  • Short-term effects of INGAP and Reg family peptides on the appearance of small β-cells clusters in non-diabetic mice.

    abstract::The Reg3 peptides INGAP-PP and human Reg3α/β (HIP) have been hypothesized to stimulate β-cell neogenesis in the pancreas. Administration of INGAP-PP has been shown to cause an increase in β-cell mass in multiple animal models, reverse streptozotocin (STZ) induced diabetes in mice and reduces HbA1c levels in type 2 dia...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.18659

    authors: Kapur R,Højfeldt TW,Højfeldt TW,Rønn SG,Karlsen AE,Heller RS

    更新日期:2012-01-01 00:00:00

  • Immunocytochemical localization of cleaved caspase-3 in pancreatic islets from type 1 diabetic subjects.

    abstract:UNLABELLED:AIMS/ HYPOTHESIS: Caspase-3 is a main effector caspase of the apoptotic cascade. Involvement of caspase-3 has been implicated in a β cell cloned cell line from type 1 diabetic subjects and in isolated islets from type 2 diabetic subjects. RESULTS:The control islets revealed cleaved caspase-3 positive cells ...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.2.1.10041

    authors: Tomita T

    更新日期:2010-01-01 00:00:00

  • Intraoperative ultrasound examination is useful for monitoring transplanted islets: a case report.

    abstract::A 39-y-old man, who had an episode of pancreatic bleeding due to chronic pancreatitis, received total pancreatectomy with islet autotransplantation (TP with IAT). Intraoperative ultrasound (US) examination was done to detect transplanted islets and evaluate the quality of US imaging. Islet isolation from the resecte...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.22384

    authors: Sakata N,Goto M,Gumpei Y,Mizuma M,Motoi F,Satomi S,Unno M

    更新日期:2012-09-01 00:00:00

  • Differences in insulin biosynthesis pathway between small and large islets do not correspond to insulin secretion.

    abstract::In a variety of mammalian species, small islets secrete more insulin per volume than large islets. This difference may be due to diffusional limitations of large islets, or inherent differences in the insulin production pathways. The purpose of this study was to identify possible differences in the early phase of gluc...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.1080/19382014.2015.1129097

    authors: Huang HH,Stehno-Bittel L

    更新日期:2015-01-01 00:00:00

  • No non-redundant function of suppressor of cytokine signaling 2 in insulin producing β-cells.

    abstract::The members of the Suppressor of Cytokine Signaling (SOCS) protein family mainly modulate the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. SOCS-1 and SOCS-3 have already been shown to influence growth and apoptosis of pancreatic beta cells. We hypothesized that SOCS-2, which is e...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.2.4.12556

    authors: Puff R,Dames P,Weise M,Göke B,Parhofer K,Lechner A

    更新日期:2010-07-01 00:00:00

  • Isolated human islets contain a distinct population of mesenchymal stem cells.

    abstract::Islet replacement is a promising approach for type-1 diabetes treatment, but the shortage of organ donors demands new sources of β-cells. The use of stem/precursor cells may represent an attractive alternative. Islet-derived stem/precursor cells (hIPC) have been isolated from human islet preparations, but neither thei...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.2.3.11449

    authors: Carlotti F,Zaldumbide A,Loomans CJ,van Rossenberg E,Engelse M,de Koning EJ,Hoeben RC

    更新日期:2010-05-01 00:00:00

  • An effective purification method using large bottles for human pancreatic islet isolation.

    abstract::The purification process is one of the most difficult procedures in pancreatic islet isolation. It was demonstrated that the standard purification method using a COBE 2991 cell processor with Ficoll density gradient solution harmed islets mechanically by high shear force. We reported that purification using large bott...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.23008

    authors: Shimoda M,Itoh T,Iwahashi S,Takita M,Sugimoto K,Kanak MA,Chujo D,Naziruddin B,Levy MF,Grayburn PA,Matsumoto S

    更新日期:2012-11-01 00:00:00

  • Parental high-fat programming of offspring development, health and β-cells.

    abstract::Recent studies extend the concept of developmental and adaptive plasticity to include a paternal role in the programming of metabolic disease, including diabetes. Parents greatly influence the development and health of their offspring. Although genetic imprinting plays a major role in determining offspring health outc...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.3.3.15420

    authors: Cerf ME

    更新日期:2011-05-01 00:00:00

  • Differential synthesis and action of TGFß superfamily ligands in mouse and rat islets.

    abstract::Members of the TGFß superfamily, including activins and TGFß, modulate glucose-stimulated insulin secretion (GSIS) in vitro using rat islets while genetic manipulations that reduce TGFß superfamily signaling in vivo in mice produced hypoplastic islets and/or hyperglycemia. Moreover, deletion of Fstl3, an antagonist of...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.3.6.18013

    authors: Brown ML,Kimura F,Bonomi LM,Ungerleider NA,Schneyer AL

    更新日期:2011-11-01 00:00:00

  • Systematic review of islet cryopreservation.

    abstract::Pancreatic islet transplantation is being extensively researched as an alternative treatment for type 1 diabetic patients. This treatment is currently limited by temporal mismatch, between the availability of pancreas and isolated islets from deceased organ donor, and the recipient's need for freshly isolated islets. ...

    journal_title:Islets

    pub_type: 历史文章,杂志文章

    doi:10.1080/19382014.2017.1405202

    authors: Kojayan GG,Alexander M,Imagawa DK,Lakey JRT

    更新日期:2018-01-02 00:00:00

  • Rab-geranylgeranyl transferase regulates glucose-stimulated insulin secretion from pancreatic β cells.

    abstract::A growing body of evidence implicates essential roles for small molecular weight G-proteins (e.g., Cdc42, Rac1, Arf6 and Rab3A and Rab27A) in islet β-cell function including glucose-stimulated insulin secretion (GSIS). One of the known mechanisms for optimal activation of small G-proteins involves post-translational p...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.22538

    authors: Arora DK,Syed I,Machhadieh B,McKenna CE,Kowluru A

    更新日期:2012-09-01 00:00:00

  • Factors affecting islet graft embolization in the liver of diabetic mice.

    abstract::BACKGROUND: Embolic occlusion of the portal vein due to islet transplantation is one of the major reasons for reduced survival of transplanted islets. In this study, we examined the location of islets as well as the correlation between islet and portal vein size after intraportal islet transplantation and evaluated li...

    journal_title:Islets

    pub_type: 杂志文章

    doi:

    authors: Sakata N,Obenaus A,Chan N,Mace J,Chinnock R,Hathout E

    更新日期:2009-07-01 00:00:00

  • Neurogenin3: a master regulator of pancreatic islet differentiation and regeneration.

    abstract::The basic helix-loop-helix transcription factor neurogenin-3 (Ngn3, Neurog3) is critical for the development of the endocrine cells of the islets. Either disrupted or forced expression of Ngn3 early in mouse pancreas development abrogates the formation of islets. The successive waves of Ngn3 expression that occur duri...

    journal_title:Islets

    pub_type: 杂志文章,评审

    doi:10.4161/isl.1.3.9877

    authors: Rukstalis JM,Habener JF

    更新日期:2009-11-01 00:00:00

  • Islet versus pancreas transplantation in Brazil: Defining criteria for pancreas allocation decision.

    abstract:BACKGROUND:Many studies have evaluated whether there are characteristics related to pancreas donors and the islet isolation process that can influence pancreatic islet yield. However, this analysis has not yet been performed in Brazil, one of the world leaders in whole pancreas organ transplantation (WOPT), where pancr...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.3.6.17908

    authors: Sá GP,Sogayar MC,Eliaschewitz FG,Genzini T,Letrinta R,Onari ES,Mantovani M,Labriola L,Matos D,Lopes-Filho GJ,Gonzalez AM,Mares-Guia TR

    更新日期:2011-11-01 00:00:00

  • A novel fluorescence imaging approach for comparative measurements of pancreatic islet function in vitro.

    abstract::Pancreatic islet dysfunction is a key element in the development of type 2 diabetes. Determining possible early warning signs of dysfunction is thus important to determining the underlying causes of diabetes. We describe an improved fluorescent imaging approach to detect potential islet dysfunction. Using Cell Tracker...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.3.1.14133

    authors: Corbin KL,Hall TE,Haile R,Nunemaker CS

    更新日期:2011-01-01 00:00:00

  • GSK-3 inactivation or depletion promotes β-cell replication via down regulation of the CDK inhibitor, p27 (Kip1).

    abstract::Diabetes (T1DM and T2DM) is characterized by a deficit in β-cell mass. A broader understanding of human β-cell replication mechanism is thus important to increase β-cell proliferation for future therapeutic interventions. Here, we show that p27 (Kip1), a CDK inhibitor, is expressed abundantly in isolated adult human i...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.3.1.14435

    authors: Stein J,Milewski WM,Hara M,Steiner DF,Dey A

    更新日期:2011-01-01 00:00:00

  • Blockade of both B7-H4 and CTLA-4 co-signaling pathways enhances mouse islet allograft survival.

    abstract::Costimulation blockade is an effective way to prevent allograft rejection. In this study, we tested the efficacy of two negative co-signaling molecules in protecting islet allograft function. We used local expression of B7-H4 by adenoviral transduction of islets (Ad-B7-H4) and systemic administration of CTLA-4.Ig to i...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.21239

    authors: Wang X,Hao J,Metzger DL,Mui A,Lee IF,Akhoundsadegh N,Chen CL,Ou D,Ao Z,Verchere CB,Warnock GL

    更新日期:2012-07-01 00:00:00

  • β-cell dedifferentiation in diabetes is important, but what is it?

    abstract::This commentary discusses the concept of β-cell dedifferentiation in diabetes, which is important but not well defined. A broad interpretation is that a state of differentiation has been lost, which means changes in gene expression as well as in structural and functional elements. Thus, a fully mature healthy β cell w...

    journal_title:Islets

    pub_type: 杂志文章,评审

    doi:10.4161/isl.27494

    authors: Weir GC,Aguayo-Mazzucato C,Bonner-Weir S

    更新日期:2013-09-01 00:00:00

  • Pancreatic and duodenal homeobox-1 nuclear localization is regulated by glucose in dispersed rat islets but not in insulin-secreting cell lines.

    abstract::The transcription factor Pancreatic and Duodenal Homeobox-1 (PDX-1) plays a major role in the development and function of pancreatic β-cells and its mutation results in diabetes. In adult β-cells, glucose stimulates transcription of the insulin gene in part by regulating PDX-1 expression, stability and activity. Gluco...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/19382014.2014.982376

    authors: Semache M,Ghislain J,Zarrouki B,Tremblay C,Poitout V

    更新日期:2014-01-01 00:00:00

  • Identification of genes selectively disallowed in the pancreatic islet.

    abstract::We have previously identified two genes, encoding lactate dehydrogenase (Ldha) and the monocarboxylate carrier, MCT1 (Slc16a1) whose expression is remarkably low in pancreatic β-cells and islets. We sought here to determine whether these may be part of a larger family of genes selectively repressed ("disallowed") in t...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.2.2.11025

    authors: Pullen TJ,Khan AM,Barton G,Butcher SA,Sun G,Rutter GA

    更新日期:2010-03-01 00:00:00

  • Metabolic syndrome induces changes in KATP-channels and calcium currents in pancreatic β-cells.

    abstract::Metabolic syndrome (MS) can be defined as a group of signs that increases the risk of developing type 2 diabetes mellitus (DM2). These signs include obesity, hyperinsulinemia and insulin resistance. We are interested in the mechanisms that trigger hyperinsulinemia as a step to understand how β cells fail in DM2. Pancr...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.21374

    authors: Velasco M,Larqué C,Gutiérrez-Reyes G,Arredondo R,Sanchez-Soto C,Hiriart M

    更新日期:2012-07-01 00:00:00

  • The impact of anti-inflammatory cytokines on the pancreatic β-cell.

    abstract::Considerable efforts have been invested to understand the mechanisms by which pro-inflammatory cytokines mediate the demise of β-cells in type 1 diabetes but much less attention has been paid to the role of anti-inflammatory cytokines as potential cytoprotective agents in these cells. Despite this, there is increasing...

    journal_title:Islets

    pub_type: 杂志文章,评审

    doi:10.4161/19382014.2014.950547

    authors: Russell MA,Morgan NG

    更新日期:2014-01-01 00:00:00

  • Bioengineering a highly vascularized matrix for the ectopic transplantation of islets.

    abstract::Islet transplantation is a promising treatment for Type 1 diabetes; however limitations of the intra-portal site and poor revascularization of islets must be overcome. We hypothesize that engineering a highly vascularized collagen-based construct will allow islet graft survival and function in alternative sites. In th...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.27175

    authors: Ellis CE,Vulesevic B,Suuronen E,Yeung T,Seeberger K,Korbutt GS

    更新日期:2013-09-01 00:00:00

  • Effect of inborn pancreatic islet deficit in the Munich Wister Frömter rat.

    abstract::The total mass of pancreatic islet cells is a critical factor in glucose metabolic control. The aim of the present study was to investigate whether in the Munich Wistar Frömter (MWF) rat, beside a reduction in the number of nephrons, there are also alterations in the number of pancreatic islets and of β cell mass. We ...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.2.5.13178

    authors: Figliuzzi M,Bonandrini B,Cattaneo I,Remuzzi G,Remuzzi A

    更新日期:2010-09-01 00:00:00

  • Activation of apocynin-sensitive NADPH oxidase (Nox2) activity in INS-1 832/13 cells under glucotoxic conditions.

    abstract::Several lines of recent evidence provided compelling evidence to suggest increased generation of reactive oxygen species (ROS) as causal for mitochondrial dysregulation and apoptosis in islet β-cells exposed to noxious stimuli including high glucose, lipids and proinflammatory cytokines. Studies along these lines are ...

    journal_title:Islets

    pub_type: 杂志文章

    doi:10.4161/isl.25058

    authors: Mohammed AM,Kowluru A

    更新日期:2013-05-01 00:00:00