scholarly journals Innervation modulates the functional connectivity between pancreatic endocrine cells

2020 ◽  
Author(s):  
Yu Hsuan Carol Yang ◽  
Linford J.B. Briant ◽  
Christopher Raab ◽  
Sri Teja Mullapudi ◽  
Hans-Martin Maischein ◽  
...  
Keyword(s):  
Cell Activity ◽  
Cell Types ◽  
Vital Role ◽  
Imaging Model ◽  
Pancreatic Endocrine Cells ◽  
Glucose Exposure ◽  
Delta Cell ◽  
Islet Cell Types ◽  
Delta Cells

AbstractDirect modulation of pancreatic endocrine cell activity by autonomic innervation has been debated. To resolve this question, we established an in vivo imaging model which also allows chronic and acute neuromodulation. Starting at a stage when zebrafish islet architecture is reminiscent of that in adult rodents, we imaged calcium dynamics simultaneously in multiple islet cell types. We first find that activity coupling between beta cells increases upon glucose exposure. Surprisingly, glucose exposure also increases alpha-alpha, alpha-beta and beta-delta coordination. We further show that both chronic and acute loss of nerve activity diminish activity coupling, as observed upon gap junction depletion. Notably, chronic loss of innervation severely disrupts delta cell activity, suggesting that delta cells receive innervation which coordinates its output. Overall, these data show that innervation plays a vital role in the establishment and maintenance of homotypic and heterotypic cellular connectivity in pancreatic islets, a process critical for islet function.

scholarly journals Role of Luteal Glucocorticoid Metabolism during Maternal Recognition of Pregnancy in Women

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5769-5779 ◽  
Author(s):  
Michelle Myers ◽  
M. Christy Lamont ◽  
Sander van den Driesche ◽  
Nirmala Mary ◽  
K. Joo Thong ◽  
...  
Keyword(s):  
Cell Activity ◽  
Tissue Remodeling ◽  
Cell Types ◽  
Endocrine Gland ◽  
Steroidogenic Cell ◽  
Luteal Tissue ◽  
Maternal Recognition Of Pregnancy

The human corpus luteum (hCL) is an active, transient, and dynamic endocrine gland. It will experience extensive tissue and vascular remodeling followed by 1) demise of the whole gland without any apparent scarring or 2) maintenance of structural and functional integrity dependent on conceptus-derived human chorionic gonadotropin (hCG). Because cortisol has well-characterized roles in tissue remodeling and repair, we hypothesized that it may have a role in controlling luteal dissolution during luteolysis and would be locally produced toward the end of the luteal cycle. Glucocorticoid-metabolizing enzymes [11β-hydroxysteroid dehydrogenase (11βHSD) types 1 and 2] and the glucocorticoid receptor (GR) were assessed in hCL and cultures of luteinized granulosa cells (LGC) using immunofluorescence and quantitative RT-PCR. Furthermore, the effect of cortisol on steroidogenic cell survival and fibroblast-like cell activity was explored in vitro. The hCL expressed 11βHSD isoenzymes in LGC and nuclear GR in several cell types. hCG up-regulated the expression and activity of 11βHSD type 1 (P < 0.05) and down-regulated type 2 enzyme (P < 0.05) in vitro and tended to do the same in vivo. Cortisol increased the survival of LGC treated with RU486 (P < 0.05) and suppressed the activity of a proteolytic enzyme associated with luteolysis in fibroblast-like cells (P < 0.05). Our results suggest that, rather than during luteolysis, it is luteal rescue with hCG that is associated with increased local cortisol generation by 11βHSD type 1. Locally generated cortisol may therefore act on the hCL through GR to have a luteotropic role in the regulation of luteal tissue remodeling during maternal recognition of pregnancy.

scholarly journals Group B Coxsackievirus Diabetogenic Phenotype Correlates with Replication Efficiency

2006 ◽  
Vol 80 (11) ◽  
pp. 5637-5643 ◽  
Author(s):  
Toru Kanno ◽  
Kisoon Kim ◽  
Ken Kono ◽  
Kristen M. Drescher ◽  
Nora M. Chapman ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Cultures ◽  
Virulent Strain ◽  
Nod Mice ◽  
Cell Types ◽  
Rapid Onset ◽  
Infectious Dose ◽  
Group B ◽  
Islet Cell Types

ABSTRACT Group B coxsackieviruses can initiate rapid onset type 1 diabetes (T1D) in old nonobese diabetic (NOD) mice. Inoculating high doses of poorly pathogenic CVB3/GA per mouse initiated rapid onset T1D. Viral protein was detectable in islets shortly after inoculation in association with beta cells as well as other primary islet cell types. The virulent strain CVB3/28 replicated to higher titers more rapidly than CVB3/GA in the pancreas and in established beta cell cultures. Exchange of 5′-nontranslated regions between the two CVB3 strains demonstrated a variable impact on replication in beta cell cultures and suppression of in vivo replication for both strains. While any CVB strain may be able to induce T1D in prediabetic NOD mice, T1D onset is linked both to the viral replication rate and infectious dose.

scholarly journals Chandelier cell anatomy and function reveal a variably distributed but common signal

2020 ◽  
Author(s):  
Casey M. Schneider-Mizell ◽  
Agnes L. Bodor ◽  
Forrest Collman ◽  
Derrick Brittain ◽  
Adam A. Bleckert ◽  
...  
Keyword(s):  
Large Scale ◽  
Pyramidal Neurons ◽  
Cell Activity ◽  
Cortical Cell ◽  
Cell Types ◽  
Structural Features ◽  
Target Neuron ◽  
Chandelier Cell ◽  
Chandelier Cells

AbstractThe activity and connectivity of inhibitory cells has a profound impact on the operation of neuronal networks. While the average connectivity of many inhibitory cell types has been characterized, we still lack an understanding of how individual interneurons distribute their synapses onto their targets and how heterogeneous the inhibition is onto different individual excitatory neurons. Here, we use large-scale volumetric electron microscopy (EM) and functional imaging to address this question for chandelier cells in layer 2/3 of mouse visual cortex. Using dense morphological reconstructions from EM, we mapped the complete chandelier input onto 153 pyramidal neurons. We find that the number of input synapses is highly variable across the population, but the variability is correlated with structural features of the target neuron: soma depth, soma size, and the number of perisomatic synapses received. Functionally, we found that chandelier cell activity in vivo was highly correlated and tracks pupil diameter, a proxy for arousal state. We propose that chandelier cells provide a global signal whose strength is individually adjusted for each target neuron. This approach, combining comprehensive structural analysis with functional recordings of identified cell types, will be a powerful tool to uncover the wiring rules across the diversity of cortical cell types.

Therapeutic potential of galectin-1 and galectin-3 in autoimmune diseases

2021 ◽  
Vol 27 ◽  
Author(s):  
Yi-Sheng He ◽  
Yu-Qian Hu ◽  
Kun Xiang ◽  
Yue Chen ◽  
Ya-Ting Feng ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Cell Activity ◽  
Vital Role ◽  
Promising Therapeutic Target ◽  
Galectin 3

: Galectins are a highly conserved protein family that binds to β-galactosides. Different members of this family play a variety of biological functions in physiological and pathological processes such as angiogenesis, regulation of immune cell activity, and cell adhesion. Galectins are widely distributed and play a vital role both inside and outside cells. It can regulate homeostasis and immune function in vivo through mechanisms such as apoptosis. Recent studies indicate that galectins exhibit pleiotropic roles in inflammation. Furthermore, emerging studies have found that galectins are involved in the occurrence and development of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D) and systemic sclerosis (SSc) by regulating cell adhesion, apoptosis, and other mechanisms. This review will briefly discuss the biological characteristics of the two most widely expressed and extensively explored members of the galectin family, galectin-1 and galectin-3, as well as their pathogenetic and therapeutic roles in autoimmune diseases. These information may provide a novel and promising therapeutic target for autoimmune diseases.

scholarly journals In Vivo Chemical Screen in Zebrafish Embryos Identifies Regulators of Hematopoiesis Using a Semiautomated Imaging Assay

2016 ◽  
Vol 21 (9) ◽  
pp. 956-964 ◽  
Author(s):  
Guruchandar Arulmozhivarman ◽  
Martin Stöter ◽  
Marc Bickle ◽  
Martin Kräter ◽  
Manja Wobus ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Screening Method ◽  
Cell Activity ◽  
Cell Types ◽  
Hematopoietic Stem ◽  
Drug Candidates

Hematopoietic stem and progenitor cells (HSPCs) generate all cell types of the blood and are crucial for homeostasis of all blood lineages in vertebrates. Hematopoietic stem cell transplantation (HSCT) is a rapidly evolving technique that offers potential cure for hematologic cancers, such as leukemia or lymphoma. HSCT may be autologous or allogenic. Successful HSCT depends critically on the abundance of engraftment-competent HSPCs, which are currently difficult to obtain in large numbers. Therefore, finding compounds that enhance either the number or the activity of HSPCs could improve prognosis for patients undergoing HSCT and is of great clinical interest. We developed a semiautomated screening method for whole zebrafish larvae using conventional liquid handling equipment and confocal microscopy. Applying this pipeline, we screened 550 compounds in triplicate for proliferation of HSPCs in vivo and identified several modulators of hematopoietic stem cell activity. One identified hit was valproic acid (VPA), which was further validated as a compound that expands and maintains the population of HSPCs isolated from human peripheral blood ex vivo. In summary, our in vivo zebrafish imaging screen identified several potential drug candidates with clinical relevance and could easily be further expanded to screen more compounds.

scholarly journals Osteolineage niche cells initiate hematopoietic stem cell mobilization

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 519-531 ◽  
Author(s):  
Shane R. Mayack ◽  
Amy J. Wagers
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Cell Activity ◽  
Direct Interaction ◽  
Cell Types ◽  
Hematopoietic Stem ◽  
Functional Changes ◽  
In Vivo Experiments ◽  
Cell Mobilization

Abstract Recent studies have implicated bone-lining osteoblasts as important regulators of hematopoietic stem cell (HSC) self-renewal and differentiation; however, because much of the evidence supporting this notion derives from indirect in vivo experiments, which are unavoidably complicated by the presence of other cell types within the complex bone marrow milieu, the sufficiency of osteoblasts in modulating HSC activity has remained controversial. To address this, we prospectively isolated mouse osteoblasts, using a novel flow cytometry–based approach, and directly tested their activity as HSC niche cells and their role in cyclophosphamide/granulocyte colony-stimulating factor (G-CSF)–induced HSC proliferation and mobilization. We found that osteoblasts expand rapidly after cyclophosphamide/G-CSF treatment and exhibit phenotypic and functional changes that directly influence HSC proliferation and maintenance of reconstituting potential. Effects of mobilization on osteoblast number and function depend on the function of ataxia telangiectasia mutated (ATM), the product of the Atm gene, demonstrating a new role for ATM in stem cell niche activity. These studies demonstrate that signals from osteoblasts can directly initiate and modulate HSC proliferation in the context of mobilization. This work also establishes that direct interaction with osteolineage niche cells, in the absence of additional environmental inputs, is sufficient to modulate stem cell activity.

Side population cells and Bcrp1 expression in lung

2003 ◽  
Vol 285 (1) ◽  
pp. L97-L104 ◽  
Author(s):  
Ross Summer ◽  
Darrell N. Kotton ◽  
Xi Sun ◽  
Bei Ma ◽  
Kathleen Fitzsimmons ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Smooth Muscle ◽  
Stem Cell ◽  
Side Population ◽  
Cell Activity ◽  
Cell Types ◽  
Mouse Lung ◽  
Cancer Resistance ◽  
Hoechst Dye

Side population (SP) cells are a rare subset of cells found in various tissues that are highly enriched for stem cell activity. SP cells can be isolated by dual-wavelength flow cytometry because of their capacity to efflux Hoechst dye, a process mediated by the ATP-binding cassette transporter breast cancer resistance protein (Bcrp) 1. By performing flow cytometry of enzymedigested mouse lung stained with Hoechst dye, we found that SP cells comprise 0.03–0.07% of total lung cells and are evenly distributed in proximal and distal lung regions. By RT-PCR, we found that lung SP cells express hepatocyte nuclear factor-3β, but not thyroid transcription factor-1. Surface marker analysis revealed lung SP cells to be stem cell antigen 1 positive, Bcrp1 positive, lineage marker negative, and heterogeneous at the CD45 locus. As expected, we did not detect lung SP cells in Bcrp1-deficient animals. We, therefore, employed nonisotopic in situ hybridization and immunostaining for Bcrp1 as a strategy to localize these cells in vivo. Expression was observed in distinct lung cell types: bronchial and vascular smooth muscle cells and round cells within the distal air space. We confirmed the expression of Bcrp1 in primary bronchial smooth muscle cell cultures (BSMC) and in lavaged distal airway cells, but neither possessed the capacity to efflux Hoechst dye. In BSMC, Bcrp1 was localized to an intracellular compartment, suggesting that the molecular site of Bcrp1 expression regulates SP phenotype.

scholarly journals Structure and function of axo-axonic inhibition

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Casey M Schneider-Mizell ◽  
Agnes L Bodor ◽  
Forrest Collman ◽  
Derrick Brittain ◽  
Adam Bleckert ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Large Scale ◽  
Cell Activity ◽  
Cell Types ◽  
Structural Features ◽  
Inhibitory Neurons ◽  
Target Cells ◽  
Population Activity ◽  
Chandelier Cells

Inhibitory neurons in mammalian cortex exhibit diverse physiological, morphological, molecular and connectivity signatures. While considerable work has measured the average connectivity of several interneuron classes, there remains a fundamental lack of understanding of the connectivity distribution of distinct inhibitory cell types with synaptic resolution, how it relates to properties of target cells and how it affects function. Here, we used large-scale electron microscopy and functional imaging to address these questions for chandelier cells in layer 2/3 of the mouse visual cortex. With dense reconstructions from electron microscopy, we mapped the complete chandelier input onto 153 pyramidal neurons. We found that synapse number is highly variable across the population and is correlated with several structural features of the target neuron. This variability in the number of axo-axonic ChC synapses is higher than the variability seen in perisomatic inhibition. Biophysical simulations show that the observed pattern of axo-axonic inhibition is particularly effective in controlling excitatory output when excitation and inhibition are co-active. Finally, we measured chandelier cell activity in awake animals using a cell-type specific calcium imaging approach and saw highly correlated activity across chandelier cells. In the same experiments, in vivo chandelier population activity correlated with pupil dilation, a proxy for arousal. Together these results suggest that chandelier cells provide a circuit-wide signal whose strength is adjusted relative to the properties of target neurons.

scholarly journals An in vivo RNAi screen uncovers the role of AdoR signaling and adenosine deaminase in controlling intestinal stem cell activity

2019 ◽  
Vol 117 (1) ◽  
pp. 464-471
Author(s):  
Chiwei Xu ◽  
Brian Franklin ◽  
Hong-Wen Tang ◽  
Yannik Regimbald-Dumas ◽  
Yanhui Hu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adenosine Deaminase ◽  
Tissue Damage ◽  
Cell Activity ◽  
Cell Types ◽  
Major Effect ◽  
Rnai Screen ◽  
Intestinal Stem Cell ◽  
Extracellular Adenosine

Metabolites are increasingly appreciated for their roles as signaling molecules. To dissect the roles of metabolites, it is essential to understand their signaling pathways and their enzymatic regulations. From an RNA interference (RNAi) screen for regulators of intestinal stem cell (ISC) activity in theDrosophilamidgut, we identifiedadenosine receptor(AdoR) as a top candidate gene required for ISC proliferation. We demonstrate that Ras/MAPK and Protein Kinase A (PKA) signaling act downstream of AdoR and that Ras/MAPK mediates the major effect of AdoR on ISC proliferation. Extracellular adenosine, the ligand for AdoR, is a small metabolite that can be released by various cell types and degraded in the extracellular space by secreted adenosine deaminase. Interestingly, down-regulation ofadenosine deaminase-related growth factor A(Adgf-A) from enterocytes is necessary for extracellular adenosine to activate AdoR and induce ISC overproliferation. AsAdgf-Aexpression and its enzymatic activity decrease following tissue damage, our study provides important insights into how the enzymatic regulation of extracellular adenosine levels under tissue-damage conditions facilitates ISC proliferation.

scholarly journals Reconstructing human pancreatic differentiation by mapping specific cell populations during development

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Cyrille Ramond ◽  
Nicolas Glaser ◽  
Claire Berthault ◽  
Jacqueline Ameri ◽  
Jeannette Schlichting Kirkegaard ◽  
...  
Keyword(s):  
Endocrine Cells ◽  
Cell Types ◽  
Specific Cell ◽  
In Vitro Differentiation ◽  
Pancreatic Cell ◽  
Pancreatic Differentiation ◽  
Endocrine Differentiation ◽  
Pancreatic Endocrine Cells

Information remains scarce on human development compared to animal models. Here, we reconstructed human fetal pancreatic differentiation using cell surface markers. We demonstrate that at 7weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate into the acinar, ductal or endocrine lineages. Development towards the acinar lineage is paralleled by an increase in GP2 expression. Conversely, a subset of the GP2+ population undergoes endocrine differentiation by down-regulating GP2 and CD142 and turning on NEUROG3, a marker of endocrine differentiation. Endocrine maturation progresses by up-regulating SUSD2 and lowering ECAD levels. Finally, in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work paves the way to extend our understanding of the origin of mature human pancreatic cell types and how such lineage decisions are regulated.

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