scholarly journals The Function of Lgr5+ Cells in the Gastric Antrum Does Not Require Fzd7 or Myc In Vivo

Biomedicines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 50 ◽  
Author(s):  
Dustin Flanagan ◽  
Nick Barker ◽  
Matthias Ernst ◽  
Elizabeth Vincan ◽  
Toby Phesse
Keyword(s):  
Stem Cells ◽  
Target Gene ◽  
Status Quo ◽  
Gastric Antrum ◽  
Cell Surface Receptor ◽  
Intestinal Stem Cells ◽  
Epithelial Homeostasis ◽  
Surface Receptor ◽  
Gastric Cancer Patients

The extreme chemical and mechanical forces endured by the gastrointestinal tract drive a constant renewal of the epithelial lining. Stem cells of the intestine and stomach, marked by the cell surface receptor Lgr5, preserve the cellular status-quo of their respective tissues through receipt and integration of multiple cues from the surrounding niche. Wnt signalling is a critical niche component for gastrointestinal stem cells and we have previously shown that the Wnt receptor, Frizzled-7 (Fzd7), is required for gastric homeostasis and the function of Lgr5+ intestinal stem cells. Additionally, we have previously shown a requirement for the Wnt target gene Myc in intestinal homeostasis, regeneration and tumourigenesis. However, it is unknown whether Fzd7 or Myc have conserved functions in gastric Lgr5+ stem cells. Here we show that gastric Lgr5+ stem cells do not require Fzd7 or Myc and are able to maintain epithelial homeostasis, highlighting key differences in the way Wnt regulates homeostasis and Lgr5+ stem cells in the stomach compared to the intestinal epithelium. Furthermore, deletion of Myc throughout the epithelium of the gastric antrum has no deleterious effects suggesting therapeutic targeting of Myc in gastric cancer patients will be well tolerated by the surrounding normal tissue.

scholarly journals Endocytic Delivery of Vancomycin Mediated by a Synthetic Cell Surface Receptor:  Rescue of Bacterially Infected Mammalian Cells and Tissue Targeting In Vivo

2007 ◽  
Vol 129 (2) ◽  
pp. 268-269 ◽  
Author(s):  
Siwarutt Boonyarattanakalin ◽  
Jianfang Hu ◽  
Sheryl A. Dykstra-Rummel ◽  
Avery August ◽  
Blake R. Peterson
Keyword(s):  
Cell Surface ◽  
Mammalian Cells ◽  
Cell Surface Receptor ◽  
Synthetic Cell ◽  
Tissue Targeting ◽  
Surface Receptor

scholarly journals Porcine Breast Extracellular Matrix Hydrogel for Spatial Tissue Culture

2018 ◽  
Vol 19 (10) ◽  
pp. 2912 ◽  
Author(s):  
Girdhari Rijal ◽  
Jing Wang ◽  
Ilhan Yu ◽  
David Gang ◽  
Roland Chen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Human Mammary Epithelial Cell ◽  
Tumor Formation ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Breast Diseases ◽  
Porous Scaffolds ◽  
Ecm Proteins ◽  
Surface Receptor

Porcine mammary fatty tissues represent an abundant source of natural biomaterial for generation of breast-specific extracellular matrix (ECM). Here we report the extraction of total ECM proteins from pig breast fatty tissues, the fabrication of hydrogel and porous scaffolds from the extracted ECM proteins, the structural properties of the scaffolds (tissue matrix scaffold, TMS), and the applications of the hydrogel in human mammary epithelial cell spatial cultures for cell surface receptor expression, metabolomics characterization, acini formation, proliferation, migration between different scaffolding compartments, and in vivo tumor formation. This model system provides an additional option for studying human breast diseases such as breast cancer.

scholarly journals Extracellular interactions and ligand degradation shape the nodal morphogen gradient

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Yin Wang ◽  
Xi Wang ◽  
Thorsten Wohland ◽  
Karuna Sampath
Keyword(s):  
Correlation Spectroscopy ◽  
Cell Surface Receptor ◽  
Morphogen Gradient ◽  
Axis Formation ◽  
Cellular Interactions ◽  
Fluorescence Correlation ◽  
Selective Ligand ◽  
Surface Receptor ◽  
First Time

The correct distribution and activity of secreted signaling proteins called morphogens is required for many developmental processes. Nodal morphogens play critical roles in embryonic axis formation in many organisms. Models proposed to generate the Nodal gradient include diffusivity, ligand processing, and a temporal activation window. But how the Nodal morphogen gradient forms in vivo remains unclear. Here, we have measured in vivo for the first time, the binding affinity of Nodal ligands to their major cell surface receptor, Acvr2b, and to the Nodal inhibitor, Lefty, by fluorescence cross-correlation spectroscopy. We examined the diffusion coefficient of Nodal ligands and Lefty inhibitors in live zebrafish embryos by fluorescence correlation spectroscopy. We also investigated the contribution of ligand degradation to the Nodal gradient. We show that ligand clearance via degradation shapes the Nodal gradient and correlates with its signaling range. By computational simulations of gradient formation, we demonstrate that diffusivity, extra-cellular interactions, and selective ligand destruction collectively shape the Nodal morphogen gradient.

scholarly journals A ligand-based system for receptor-specific delivery of proteins

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mariano Maffei ◽  
Chiara Morelli ◽  
Ellie Graham ◽  
Stefano Patriarca ◽  
Laura Donzelli ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Protein Delivery ◽  
Genetic Diseases ◽  
Cell Surface Receptor ◽  
Viral Gene ◽  
Promising Alternative ◽  
Large Proteins ◽  
Reporter Mice ◽  
Surface Receptor

AbstractGene delivery using vector or viral-based methods is often limited by technical and safety barriers. A promising alternative that circumvents these shortcomings is the direct delivery of proteins into cells. Here we introduce a non-viral, ligand-mediated protein delivery system capable of selectively targeting primary skin cells in-vivo. Using orthologous self-labelling tags and chemical cross-linkers, we conjugate large proteins to ligands that bind their natural receptors on the surface of keratinocytes. Targeted CRE-mediated recombination was achieved by delivery of ligand cross-linked CRE protein to the skin of transgenic reporter mice, but was absent in mice lacking the ligand’s cell surface receptor. We further show that ligands mediate the intracellular delivery of Cas9 allowing for CRISPR-mediated gene editing in the skin more efficiently than adeno-associated viral gene delivery. Thus, a ligand-based system enables the effective and receptor-specific delivery of large proteins and may be applied to the treatment of skin-related genetic diseases.

In vitro and in vivo growth of intestinal stem cells using a novel scaffold in the generation of an artificial intestine

2013 ◽  
Vol 217 (3) ◽  
pp. S144-S145 ◽  
Author(s):  
Shahab Shaffiey ◽  
Hongpeng Jia ◽  
Cait Costello ◽  
Greg Gibson ◽  
Simon Watkins ◽  
...  
Keyword(s):  
Stem Cells ◽  
Intestinal Stem Cells ◽  
In Vivo Growth ◽  
Novel Scaffold

Sialylation of the Sialic Acid Binding Lectin Sialoadhesin Regulates Its Ability to Mediate Cell Adhesion

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1245-1252 ◽  
Author(s):  
Yvonne C. Barnes ◽  
Tim P. Skelton ◽  
Ivan Stamenkovic ◽  
Dennis C. Sgroi
Keyword(s):  
Sialic Acid ◽  
Inhibitory Effect ◽  
Binding Activity ◽  
Cell Surface Receptor ◽  
Common Mechanism ◽  
Specific Cell ◽  
Sialic Acid Binding ◽  
Surface Receptor ◽  
Mediate Cell

The macrophage-specific cell surface receptor sialoadhesin, which is a member of the newly recognized family of sialic acid binding lectins called siglecs, binds glycoprotein and glycolipid ligands containing a2-3–linked sialic acid on the surface of several leukocyte subsets. Recently, the sialic acid binding activity of the siglec CD22 has been demonstrated to be regulated by sialylation of the CD22 receptor molecule. In the present work, we show that desialylation of in vivo macrophage sialylconjugates enhances sialoadhesin-mediated lectin activity. Herein, we show that receptor sialylation of soluble sialoadhesin inhibits its binding to Jurkat cell ligands, and that charge-dependent repulsion alone cannot explain this inhibition. Furthermore, we show that the inhibitory effect of sialic acid is partially dependent on the presence of an intact exocyclic side chain. These results, in conjunction with previous findings, suggest that sialylation of siglecs by specific glycosyltransferases may be a common mechanism by which siglec-mediated adhesion is regulated.

scholarly journals Minireview: A Novel Pathway of Prostacyclin Signaling—Hanging Out with Nuclear Receptors

Endocrinology ◽  
2002 ◽  
Vol 143 (9) ◽  
pp. 3207-3210 ◽  
Author(s):  
Hyunjung Lim ◽  
Sudhansu K. Dey
Keyword(s):  
Cell Surface ◽  
Nuclear Receptors ◽  
Wide Spectrum ◽  
Binding Pocket ◽  
Cell Surface Receptor ◽  
Lipoxygenase Pathway ◽  
Signaling Mechanism ◽  
Recent Developments ◽  
Surface Receptor

Abstract Prostacylin (PGI2), one of the major prostaglandins, is derived from arachidonic acid by the action of the cyclooxygenase (COX) system coupled to PGI2 synthase (PGIS). The presence of the COX-2/PGIS at the nuclear and endoplasmic reticular membrane suggests differential signaling pathways of PGI2 actions involving both cell surface and nuclear receptors. Although the signaling of PGI2 via its cell surface receptor, prostacyclin receptor (IP), is well documented in vascular biology, its action via nuclear receptors in other physiological responses is gradually being more appreciated. Peroxisomal proliferator-activated receptors (PPARs), PPARα, PPARγ, and PPARδ, though initially cloned as a family of orphan receptors, are now known for their ligand promiscuity. The ligands range from free fatty acids and their derivatives produced by the cyclooxygenase or lipoxygenase pathway to certain hypolipidemic drugs. The predisposition of PPARs to use a wide spectrum of ligands is well explained by their unusually large ligand-binding pocket. The promiscuous ligand usage by PPARs is also reflected by their involvement in various pathophysiological events. Several recent independent reports show that endogenously produced PGI2 indeed activates PPARδ in vivo, indicating that a novel signaling mechanism for this abundant eicosanoid is operative in certain systems. This review attempts to cover recent developments in nuclear actions of PGI2 in diverse biological functions.

scholarly journals Functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization

2006 ◽  
Vol 203 (1) ◽  
pp. 153-163 ◽  
Author(s):  
Gangjian Qin ◽  
Masaaki Ii ◽  
Marcy Silver ◽  
Andrea Wecker ◽  
Evelyn Bord ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Critical Role ◽  
Cell Surface Receptor ◽  
Ischemic Disease ◽  
Angiogenic Therapy ◽  
Ischemic Tissue ◽  
Surface Receptor

The cell surface receptor α4 integrin plays a critical role in the homing, engraftment, and maintenance of hematopoietic progenitor cells (HPCs) in the bone marrow (BM). Down-regulation or functional blockade of α4 integrin or its ligand vascular cell adhesion molecule-1 mobilizes long-term HPCs. We investigated the role of α4 integrin in the mobilization and homing of BM endothelial progenitor cells (EPCs). EPCs with endothelial colony-forming activity in the BM are exclusively α4 integrin–expressing cells. In vivo, a single dose of anti–α4 integrin antibody resulted in increased circulating EPC counts for 3 d. In hindlimb ischemia and myocardial infarction, systemically administered anti–α4 integrin antibody increased recruitment and incorporation of BM EPCs in newly formed vasculature and improved functional blood flow recovery and tissue preservation. Interestingly, BM EPCs that had been preblocked with anti–α4 integrin ex vivo or collected from α4 integrin–deficient mice incorporated as well as control cells into the neovasculature in ischemic sites, suggesting that α4 integrin may be dispensable or play a redundant role in EPC homing to ischemic tissue. These data indicate that functional disruption of α4 integrin may represent a potential angiogenic therapy for ischemic disease by increasing the available circulating supply of EPCs.

scholarly journals Source and Impact of the EGF Family of Ligands on Intestinal Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Helen E. Abud ◽  
Wing Hei Chan ◽  
Thierry Jardé
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Ex Vivo ◽  
Intestinal Stem Cells ◽  
Intestinal Epithelial ◽  
Neuregulin 1 ◽  
Epithelial Development ◽  
Epidermal Growth ◽  
Egf Family

Epidermal Growth Factor (EGF) has long been known for its role in promoting proliferation of intestinal epithelial cells. EGF is produced by epithelial niche cells at the base of crypts in vivo and is routinely added to the culture medium to support the growth of intestinal organoids ex vivo. The recent identification of diverse stromal cell populations that reside underneath intestinal crypts has enabled the characterization of key growth factor cues supplied by these cells. The nature of these signals and how they are delivered to drive intestinal epithelial development, daily homeostasis and tissue regeneration following injury are being investigated. It is clear that aside from EGF, other ligands of the family, including Neuregulin 1 (NRG1), have distinct roles in supporting the function of intestinal stem cells through the ErbB pathway.

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