scholarly journals Tracing the cellular basis of islet specification in mouse pancreas

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Magdalena K. Sznurkowska ◽  
Edouard Hannezo ◽  
Roberta Azzarelli ◽  
Lemonia Chatzeli ◽  
Tatsuro Ikeda ◽  
...  
Keyword(s):  
Islet Cell ◽  
Essential Role ◽  
Lineage Tracing ◽  
Secondary Transition ◽  
Β Cells ◽  
Mouse Pancreas ◽  
Cellular Basis ◽  
Endocrine Progenitors ◽  
Insight Into ◽  
Heterogeneous Size

Abstract Pancreatic islets play an essential role in regulating blood glucose level. Although the molecular pathways underlying islet cell differentiation are beginning to be resolved, the cellular basis of islet morphogenesis and fate allocation remain unclear. By combining unbiased and targeted lineage tracing, we address the events leading to islet formation in the mouse. From the statistical analysis of clones induced at multiple embryonic timepoints, here we show that, during the secondary transition, islet formation involves the aggregation of multiple equipotent endocrine progenitors that transition from a phase of stochastic amplification by cell division into a phase of sublineage restriction and limited islet fission. Together, these results explain quantitatively the heterogeneous size distribution and degree of polyclonality of maturing islets, as well as dispersion of progenitors within and between islets. Further, our results show that, during the secondary transition, α- and β-cells are generated in a contemporary manner. Together, these findings provide insight into the cellular basis of islet development.

scholarly journals Activin Enhances α- to β-Cell Transdifferentiation as a Source For β-Cells In Male FSTL3 Knockout Mice

Endocrinology ◽  
2016 ◽  
Vol 157 (3) ◽  
pp. 1043-1054 ◽  
Author(s):  
Melissa L. Brown ◽  
Danielle Andrzejewski ◽  
Amy Burnside ◽  
Alan L. Schneyer
Keyword(s):  
Cell Fate ◽  
Islet Cell ◽  
Yellow Fluorescent Protein ◽  
Lineage Tracing ◽  
Wild Type ◽  
Β Cells ◽  
Β Cell ◽  
Activin Signaling ◽  
Cell Transdifferentiation ◽  
Control Serum

Abstract Diabetes results from inadequate β-cell number and/or function to control serum glucose concentrations so that replacement of lost β-cells could become a viable therapy for diabetes. In addition to embryonic stem cell sources for new β-cells, evidence for transdifferentiation/reprogramming of non-β-cells to functional β-cells is accumulating. In addition, de-differentiation of β-cells observed in diabetes and their subsequent conversion to α-cells raises the possibility that adult islet cell fate is malleable and controlled by local hormonal and/or environmental cues. We previously demonstrated that inactivation of the activin antagonist, follistatin-like 3 (FSTL3) resulted in β-cell expansion and improved glucose homeostasis in the absence of β-cell proliferation. We recently reported that activin directly suppressed expression of critical α-cell genes while increasing expression of β-cell genes, supporting the hypothesis that activin is one of the local hormones controlling islet cell fate and that increased activin signaling accelerates α- to β-cell transdifferentiation. We tested this hypothesis using Gluc-Cre/yellow fluorescent protein (YFP) α-cell lineage tracing technology combined with FSTL3 knockout (KO) mice to label α-cells with YFP. Flow cytometry was used to quantify unlabeled and labeled α- and β-cells. We found that Ins+/YFP+ cells were significantly increased in FSTL3 KO mice compared with wild type littermates. Labeled Ins+/YFP+ cells increased significantly with age in FSTL3 KO mice but not wild type littermates. Sorting results were substantiated by counting fluorescently labeled cells in pancreatic sections. Activin treatment of isolated islets significantly increased the number of YFP+/Ins+ cells. These results suggest that α- to β-cell transdifferentiation is influenced by activin signaling and may contribute substantially to β-cell mass.

IONIC EFFECTS ON THE UPTAKE OF CHLOROMERCURIBENZENE-p-SULPHONIC ACID BY PANCREATIC ISLETS

1977 ◽  
Vol 86 (3) ◽  
pp. 552-560 ◽  
Author(s):  
Monica Söderberg ◽  
Inge-Bert Täljedal
Keyword(s):  
Pancreatic Islets ◽  
Islet Cell ◽  
Choline Chloride ◽  
Inorganic Ions ◽  
Sulphonic Acid ◽  
Cell Uptake ◽  
Β Cells ◽  
Sulphydryl Groups ◽  
Microdissected Pancreatic Islets ◽  
Ionic Effects

ABSTRACT Effects of inorganic ions on the uptake of chloromercuribenzene-p-sulphonic acid (CMBS) were studied in microdissected pancreatic islets of non-inbred ob/ob-mice. Na2SO4 stimulated the total islet cell uptake of CMBS but decreased the amount of CMBS remaining in islets after brief washing with L-cysteine. CaCl2 stimulated both the total and the cysteine-non-displaceable uptake; the stimulatory effect of CaCl2 on the cysteine-non-displaceable CMBS uptake was counteracted by Na2SO4. NaCl, KCl or choline chloride had no significant effect on the total islet cell uptake of CMBS, whereas LiCl was stimulatory. It is concluded that β-cells resemble erythrocytes in having a permeation path for CMBS that is inhibited by SO42−. By analogy with existing models of the erythrocyte membrane, it is suggested that the SO42−-sensitive path leads to sulphydryl groups controlling monovalent cationic permeability in β-cells.

scholarly journals Pancreatic β-cells express hepcidin, an iron-uptake regulatory peptide

2008 ◽  
Vol 197 (2) ◽  
pp. 241-249 ◽  
Author(s):  
Hasan Kulaksiz ◽  
Evelyn Fein ◽  
Peter Redecker ◽  
Wolfgang Stremmel ◽  
Guido Adler ◽  
...  
Keyword(s):  
Iron Uptake ◽  
Secretory Granules ◽  
Rinm5f Cells ◽  
Β Cells ◽  
Additional Source ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Vital Functions ◽  
Immunohistochemical Studies ◽  
Insight Into

Body iron is involved in various vital functions. Its uptake in the intestine is regulated by hepcidin, a bioactive peptide originally identified in plasma and urine and subsequently in the liver. In the present study, we provide evidence at the transcriptional and translational levels that hepcidin is also expressed in the pancreas of rat and man. Immunohistochemical studies localized the peptide exclusively to β-cells of the islets of Langerhans. Immunoelectron microscopical analyses revealed that hepcidin is confined to the insulin-storing β-cell secretory granules. As demonstrated in insulinoma-derived RINm5F cells, the expression of hepcidin in β-cells is regulated by iron. Based on the present findings we conclude that pancreatic islets are an additional source of the peptide hepcidin. The localization of this peptide to β-cells suggests that pancreatic β-cells may be involved in iron metabolism in addition to their genuine function in blood glucose regulation. In view of the various linked iron/glucose disorders in the pancreas, the present findings may provide an insight into the phenomenology of intriguing mutual relationships between iron and glucose metabolisms.

Insight into the practical models for prediciting the essential role of the cytochrome P450-mediated biotransformation in emodin-associated hepatotoxicity

Toxicology ◽  
2021 ◽  
Vol 462 ◽  
pp. 152930
Author(s):  
Tingting Zhang ◽  
Xiaomei He ◽  
Lanlan Sun ◽  
Dong Wang ◽  
Shuya Zhang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Essential Role ◽  
Insight Into

Immunofluorescent Staining of Mouse Pancreas for Islet Cell Mass Analysis v1

2021 ◽  
Author(s):  
Islet and Pancreas Analysis Core
Keyword(s):  
Quantitative Determination ◽  
Islet Cell ◽  
Cell Mass ◽  
Immunofluorescent Staining ◽  
Assay Method ◽  
Mass Analysis ◽  
Mouse Pancreas ◽  
Cell Composition ◽  
Diabetes Center

This SOP defines the assay method used by the Vanderbilt Diabetes Center Islet and Pancreas Analysis (IPA) Core for quantitative determination of the islet cell composition and islet cell mass of mouse pancreas by immunofluorescent staining.

scholarly journals Gpr125 identifies myoepithelial progenitors at tips of lacrimal ducts and is essential for tear film

2020 ◽  
Author(s):  
Elena Spina ◽  
Rebecca Handlin ◽  
Julia Simundza ◽  
Angela Incassati ◽  
Muneeb Faiq ◽  
...  
Keyword(s):  
Dry Eye ◽  
Essential Role ◽  
Tear Film ◽  
Lineage Tracing ◽  
Dry Eye Syndrome ◽  
Planar Polarity ◽  
Inflammatory Infiltration ◽  
Discrete Population ◽  
Signaling Domains ◽  
G Protein Coupled

AbstractGpr125, encoded by Adgra3, is an orphan adhesion G-protein coupled receptor (aGPCR) implicated in modulating Wnt signaling and planar polarity. Here we establish both physiological and pathological roles for Gpr125. We show that mice lacking Gpr125 or its signaling domains display an ocular phenotype with many hallmarks of human dry eye syndrome. These include squinting, abnormal lacrimation, mucus accumulation, swollen eyelids and inflammatory infiltration of lacrimal and meibomian glands. Utilizing a Gpr125-β-gal reporter and scRNAseq, we identify Gpr125 expression in a discrete population of cells located at the tips of migrating embryonic lacrimal ducts. By lineage tracing we show these cells function as progenitors of the adult lacrimal myoepithelium. Beyond defining an essential role for Gpr125 in tear film and identifying its utility as a marker of lacrimal progenitors, this study implicates Gpr125 in the etiology of blepharitis and dry eye syndrome, and defines novel animal models of these common maladies.

scholarly journals Establishment of human pluripotent stem cell-derived pancreatic β-like cells in the mouse pancreas

2018 ◽  
Vol 115 (15) ◽  
pp. 3924-3929 ◽  
Author(s):  
Haiting Ma ◽  
Katherine J. Wert ◽  
Dmitry Shvartsman ◽  
Douglas A. Melton ◽  
Rudolf Jaenisch
Keyword(s):  
Stem Cell ◽  
Cell Types ◽  
Human Cells ◽  
Β Cells ◽  
Orthotopic Transplantation ◽  
In Vivo Models ◽  
Pancreatic Cell ◽  
Mouse Pancreas ◽  
Ductal Cells ◽  
Neonatal Mice

Type 1 diabetes is characterized by autoimmune destruction of β cells located in pancreatic islets. However, tractable in vivo models of human pancreatic β cells have been limited. Here, we generated xenogeneic human pancreatic β-like cells in the mouse pancreas by orthotopic transplantation of stem cell-derived β (SC-β) cells into the pancreas of neonatal mice. The engrafted β-like cells expressed β cell transcription factors and markers associated with functional maturity. Engrafted human cells recruited mouse endothelial cells, suggesting functional integration. Human insulin was detected in the blood circulation of transplanted mice for months after transplantation and increased upon glucose stimulation. In addition to β-like cells, human cells expressing markers for other endocrine pancreas cell types, acinar cells, and pancreatic ductal cells were identified in the pancreata of transplanted mice, indicating that this approach allows studying other human pancreatic cell types in the mouse pancreas. Our results demonstrate that orthotopic transplantation of human SC-β cells into neonatal mice is an experimental platform that allows the generation of mice with human pancreatic β-like cells in the endogenous niche.

Overview of neuroimaging

2019 ◽  
pp. 31-44
Author(s):  
Tomasz Matys ◽  
Daniel. J. Scoffings ◽  
Tilak Das
Keyword(s):  
Essential Role ◽  
Imaging Techniques ◽  
Disease Process ◽  
Future Directions ◽  
Anatomical Imaging ◽  
Radiological Methods ◽  
Physical Principles ◽  
Insight Into ◽  
Individual Disease

Imaging plays an essential role in the diagnosis and treatment of neurosurgical conditions. This chapter discusses the basic physical principles, applications, and limitations of the main imaging techniques used in neurosurgical practice, and highlights potential future directions of functional and molecular neuroimaging. Current conventional radiological methods allow demonstration of anatomical and macroscopic pathological features of disease with excellent sensitivity and resolution. Functional imaging methods that have enabled insight into a variety of physiological and pathological phenomena are also described, and are an important first step beyond anatomical imaging towards more precise characterization of the disease process. These methods however remain generally non-specific, demonstrating changes that are common endpoints of many possible pathological pathways. This chapter also covers current neuroradiology imaging modalities that are useful in neurosurgical practice, and focuses on the general usefulness and limitations of neuroradiological methods rather than the imaging manifestations of individual disease processes, which are discussed elsewhere in this book.

Composition and function of macroencapsulated human embryonic stem cell-derived implants: comparison with clinical human islet cell grafts

2014 ◽  
Vol 307 (9) ◽  
pp. E838-E846 ◽  
Author(s):  
Evi Motté ◽  
Edit Szepessy ◽  
Krista Suenens ◽  
Geert Stangé ◽  
Myriam Bomans ◽  
...  
Keyword(s):  
Islet Cell ◽  
Endocrine Cells ◽  
Large Scale ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Embryonic Stem ◽  
Human Islet ◽  
Insulin Biosynthesis ◽  
Β Cells ◽  
C Peptide

β-Cells generated from large-scale sources can overcome current shortages in clinical islet cell grafts provided that they adequately respond to metabolic variations. Pancreatic (non)endocrine cells can develop from human embryonic stem (huES) cells following in vitro derivation to pancreatic endoderm (PE) that is subsequently implanted in immune-incompetent mice for further differentiation. Encapsulation of PE increases the proportion of endocrine cells in subcutaneous implants, with enrichment in β-cells when they are placed in TheraCyte-macrodevices and predominantly α-cells when they are alginate-microencapsulated. At posttransplant (PT) weeks 20–30, macroencapsulated huES implants presented higher glucose-responsive plasma C-peptide levels and a lower proinsulin-over-C-peptide ratio than human islet cell implants under the kidney capsule. Their ex vivo analysis showed the presence of single-hormone-positive α- and β-cells that exhibited rapid secretory responses to increasing and decreasing glucose concentrations, similar to isolated human islet cells. However, their insulin secretory amplitude was lower, which was attributed in part to a lower cellular hormone content; it was associated with a lower glucose-induced insulin biosynthesis, but not with lower glucagon-induced stimulation, which together is compatible with an immature functional state of the huES-derived β-cells at PT weeks 20–30. These data support the therapeutic potential of macroencapsulated huES implants but indicate the need for further functional analysis. Their comparison with clinical-grade human islet cell grafts sets references for future development and clinical translation.

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