scholarly journals Erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration

2013 ◽  
Vol 210 (2) ◽  
pp. 205-208 ◽  
Author(s):  
Hal E. Broxmeyer
Keyword(s):  
Cell Types ◽  
Clinical Consideration ◽  
Cell Type ◽  
Erythroid Progenitors ◽  
Chain Component ◽  
Gm Csf ◽  
Cell Tissue ◽  
Wide Range ◽  
The Common ◽  
Β Chain

Erythropoietin (EPO), a humoral regulator of erythropoiesis and replacement therapy for selected red blood cell disorders in EPO-deficient patients, has been implicated in a wide range of activities on diverse cell, tissue, and organ types. EPO signals via two receptors, one comprising EPO receptor (EPOR) homodimers and the other a heterodimer of EPOR and CD131—the common β chain component of the GM-CSF, interleukin (IL)-3, and IL-5 receptors. Ligation of EPORs triggers various signaling pathways, including the JAK2–STAT5 and MAPK–NF-κB pathways, depending both on the receptor and the target cell type. A new study in this issue reveals a novel EPO-triggered pathway involving a Spi2A serpin–lysosome–cathepsin cascade that is initiated through the homodimeric EPOR complex and is required for the survival of erythroid progenitors. A full understanding of EPO’s effects on various cell types and their potential clinical relevance requires more work on the signaling events initiated through both EPORs, the effects of other cytokines and growth factors that modulate EPO’s actions, and a comparison of the effects of full-length versus truncated forms of EPO.

scholarly journals Panoramic stitching of heterogeneous single-cell transcriptomic data

2018 ◽  
Author(s):  
Brian Hie ◽  
Bryan Bryson ◽  
Bonnie Berger
Keyword(s):  
Single Cell ◽  
Cell Types ◽  
Data Sets ◽  
Cell Type ◽  
Data Set ◽  
Wide Range ◽  
Data Set Integration ◽  
Biological Patterns ◽  
Insight Into ◽  
Comprehensive Reference

AbstractResearchers are generating single-cell RNA sequencing (scRNA-seq) profiles of diverse biological systems1–4 and every cell type in the human body.5 Leveraging this data to gain unprecedented insight into biology and disease will require assembling heterogeneous cell populations across multiple experiments, laboratories, and technologies. Although methods for scRNA-seq data integration exist6,7, they often naively merge data sets together even when the data sets have no cell types in common, leading to results that do not correspond to real biological patterns. Here we present Scanorama, inspired by algorithms for panorama stitching, that overcomes the limitations of existing methods to enable accurate, heterogeneous scRNA-seq data set integration. Our strategy identifies and merges the shared cell types among all pairs of data sets and is orders of magnitude faster than existing techniques. We use Scanorama to combine 105,476 cells from 26 diverse scRNA-seq experiments across 9 different technologies into a single comprehensive reference, demonstrating how Scanorama can be used to obtain a more complete picture of cellular function across a wide range of scRNA-seq experiments.

scholarly journals The complement of desmosomal plaque proteins in different cell types.

1985 ◽  
Vol 101 (4) ◽  
pp. 1442-1454 ◽  
Author(s):  
P Cowin ◽  
H P Kapprell ◽  
W W Franke
Keyword(s):  
Guinea Pig ◽  
Cell Types ◽  
Cardiac Cells ◽  
Myocardial Tissue ◽  
Cell Type ◽  
Wide Range ◽  
Specific Manner ◽  
A Cell ◽  
Cell Type Specific ◽  
Different Cell Types

Desmosomal plaque proteins have been identified in immunoblotting and immunolocalization experiments on a wide range of cell types from several species, using a panel of monoclonal murine antibodies to desmoplakins I and II and a guinea pig antiserum to desmosomal band 5 protein. Specifically, we have taken advantage of the fact that certain antibodies react with both desmoplakins I and II, whereas others react only with desmoplakin I, indicating that desmoplakin I contains unique regions not present on the closely related desmoplakin II. While some of these antibodies recognize epitopes conserved between chick and man, others display a narrow species specificity. The results show that proteins whose size, charge, and biochemical behavior are very similar to those of desmoplakin I and band 5 protein of cow snout epidermis are present in all desmosomes examined. These include examples of simple and pseudostratified epithelia and myocardial tissue, in addition to those of stratified epithelia. In contrast, in immunoblotting experiments, we have detected desmoplakin II only among cells of stratified and pseudostratified epithelial tissues. This suggests that the desmosomal plaque structure varies in its complement of polypeptides in a cell-type specific manner. We conclude that the obligatory desmosomal plaque proteins, desmoplakin I and band 5 protein, are expressed in a coordinate fashion but independently from other differentiation programs of expression such as those specific for either epithelial or cardiac cells.

Interaction of GM-CSF and IL-3 with the common β-chain of their receptors

1995 ◽  
Vol 57 (5) ◽  
pp. 739-746 ◽  
Author(s):  
Christopher J. Bagley ◽  
Joanna M. Woodcock ◽  
Timothy R. Hercus ◽  
M. Frances Shannon ◽  
Angel F. Lopez
Keyword(s):  
Gm Csf ◽  
The Common ◽  
Β Chain

scholarly journals Common cell type nomenclature for the mammalian brain

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jeremy A Miller ◽  
Nathan W Gouwens ◽  
Bosiljka Tasic ◽  
Forrest Collman ◽  
Cindy TJ van Velthoven ◽  
...  
Keyword(s):  
Cell Types ◽  
Data Driven ◽  
Mammalian Brain ◽  
Gene Transcript ◽  
Cell Type ◽  
Sequencing Technologies ◽  
Multiple Organs ◽  
Source Data ◽  
The Common ◽  
Common Cell

The advancement of single-cell RNA-sequencing technologies has led to an explosion of cell type definitions across multiple organs and organisms. While standards for data and metadata intake are arising, organization of cell types has largely been left to individual investigators, resulting in widely varying nomenclature and limited alignment between taxonomies. To facilitate cross-dataset comparison, the Allen Institute created the common cell type nomenclature (CCN) for matching and tracking cell types across studies that is qualitatively similar to gene transcript management across different genome builds. The CCN can be readily applied to new or established taxonomies and was applied herein to diverse cell type datasets derived from multiple quantifiable modalities. The CCN facilitates assigning accurate yet flexible cell type names in the mammalian cortex as a step toward community-wide efforts to organize multi-source, data-driven information related to cell type taxonomies from any organism.

scholarly journals CSL311, a novel, potent, therapeutic monoclonal antibody for the treatment of diseases mediated by the common β chain of the IL-3, GM-CSF and IL-5 receptors

mAbs ◽  
2015 ◽  
Vol 8 (3) ◽  
pp. 436-453 ◽  
Author(s):  
Con Panousis ◽  
Urmi Dhagat ◽  
Kirsten M. Edwards ◽  
Veronika Rayzman ◽  
Matthew P. Hardy ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Gm Csf ◽  
Therapeutic Monoclonal Antibody ◽  
The Common ◽  
Β Chain

scholarly journals Hematopoietic and nonhematopoietic cell tissue factor activates the coagulation cascade in endotoxemic mice

Blood ◽  
2010 ◽  
Vol 116 (5) ◽  
pp. 806-814 ◽  
Author(s):  
Rafal Pawlinski ◽  
Jian-Guo Wang ◽  
A. Phillip Owens ◽  
Julie Williams ◽  
Silvio Antoniak ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tissue Factor ◽  
Myeloid Cells ◽  
Cell Types ◽  
Selective Inhibition ◽  
Coagulation Cascade ◽  
Cell Type ◽  
Relative Contribution ◽  
Cell Tissue ◽  
Tf Gene

Tissue factor (TF) is the primary activator of the coagulation cascade. During endotoxemia, TF expression leads to disseminated intravascular coagulation. However, the relative contribution of TF expression by different cell types to the activation of coagulation has not been defined. In this study, we investigated the effect of either a selective inhibition of TF expression or cell type-specific deletion of the TF gene (F3) on activation of coagulation in a mouse model of endotoxemia. We found that inhibition of TF on either hematopoietic or nonhematopoietic cells reduced plasma thrombin-antithrombin (TAT) levels 8 hours after administration of bacterial lipopolysaccharide (LPS). In addition, plasma TAT levels were significantly reduced in endotoxemic mice lacking the TF gene in either myeloid cells (TFflox/flox,LysMCre mice) or in both endothelial cells (ECs) and hematopoietic cells (TFflox/flox,Tie-2Cre mice). However, deletion of the TF gene in ECs alone had no effect on LPS-induced plasma TAT levels. Similar results were observed in mice lacking TF in vascular smooth muscle cells. Finally, we found that mouse platelets do not express TF pre-mRNA or mRNA. Our data demonstrate that in a mouse model of endotoxemia activation of the coagulation cascade is initiated by TF expressed by myeloid cells and an unidentified nonhematopoietic cell type(s).

scholarly journals Defective Autophagy in Atherosclerosis: To Die or to Senesce?

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Mandy O. J. Grootaert ◽  
Lynn Roth ◽  
Dorien M. Schrijvers ◽  
Guido R. Y. De Meyer ◽  
Wim Martinet
Keyword(s):  
Cell Types ◽  
Special Focus ◽  
Oxygen Species ◽  
Cell Type ◽  
Mitochondrial Quality Control ◽  
Targeted Treatments ◽  
Wide Range ◽  
Autophagic Process ◽  
Progression Of Atherosclerosis

Autophagy is a subcellular process that plays an important role in the degradation of proteins and damaged organelles such as mitochondria (a process termed “mitophagy”) via lysosomes. It is crucial for regulating protein and mitochondrial quality control and maintaining cellular homeostasis, whereas dysregulation of autophagy has been implicated in a wide range of diseases including atherosclerosis. Recent evidence has shown that the autophagic process becomes dysfunctional during the progression of atherosclerosis, regardless of whether there are many autophagy-stimulating factors (e.g., reactive oxygen species, oxidized lipids, and cytokines) present within the atherosclerotic plaque. This review highlights the recent insights into the causes and consequences of defective autophagy in atherosclerosis, with a special focus on the role of autophagy and mitophagy in plaque macrophages, vascular smooth muscle cells (VSMCs), and endothelial cells (ECs). It has been shown that defective autophagy can promote apoptosis in macrophages but that it accelerates premature senescence in VSMCs. In the ECs, defective autophagy promotes both apoptosis and senescence. We will discuss the discrepancy between these three cell types in their response to autophagy deficiency and underline the cell type-dependent role of autophagy, which may have important implications for the efficacy of autophagy-targeted treatments for atherosclerosis.

scholarly journals Histological and histochemical characterization of the secretory cells of Choeradoplana iheringi Graff, 1899 (Platyhelminthes: Tricladida: Terricola)

2004 ◽  
Vol 64 (3a) ◽  
pp. 511-522 ◽  
Author(s):  
S. A. de Souza ◽  
A. M. Leal-Zanchet
Keyword(s):  
Secretory Cell ◽  
Basic Protein ◽  
Cell Types ◽  
Secretory Cells ◽  
Mucous Secretion ◽  
Cell Type ◽  
The Common ◽  
First Time ◽  
Histochemical Characterization

The present study aims at providing a detailed description of the histology, as well as the first histochemical characterization, of the secretory cells of the epidermis, pharynx, and copulatory organs of Choeradoplana iheringi, in order to give further support to studies on the physiology of these organs. The secretory cells are distinguished on the basis of secretion morphology and its staining properties, using trichrome methods and histochemical reactions. Four cell types open through the epidermis of Ch. iheringi, three of them secreting basic protein and a fourth containing glycosaminoglycan mucins. The epidermal lining cells store glycogen. In the pharynx, four secretory cell types were distinguished. Two types produce glycoprotein, a third type secretes basic protein, and another one produces glycosaminoglycan mucins. In the male copulatory organs, the prostatic vesicle receives four secretory cell types containing basic protein, except for one type which produces glycoprotein. The two secretory cell types opening into the male atrium secrete, respectively, glycoprotein, and glycosaminoglycan mucins. In the female copulatory organs, the female atrium and its proximal diverticulum, the vagina, receive two types of secretory cells producing, respectively, basic protein and glycosaminoglycan mucins. Another secretory cell type constitutes the so-called shell glands which open into the common glandular duct, secreting basic protein. The lining cells of the male and female atria produce a mucous secretion containing glycosaminoglycans. In addition, the lining epithelium of the female atrium presents an apical secretion of a proteic nature. The occurrence of a kind of spermatophore is reported for the first time for a species of Choeradoplana. This structure is located in the male or female atria in different specimens, and characterized by erythrophil, xanthophil, and/or mixed secretions associated with sperm.

Identification of a 14-3-3 Binding Sequence in the Common β Chain of the Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), Interleukin-3 (IL-3), and IL-5 Receptors That Is Serine-Phosphorylated by GM-CSF

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 1933-1942 ◽  
Author(s):  
F.C. Stomski ◽  
M. Dottore ◽  
W. Winnall ◽  
M.A. Guthridge ◽  
J. Woodcock ◽  
...  
Keyword(s):  
Binding Site ◽  
Signaling Molecules ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
The Common ◽  
Macrophage Colony ◽  
Β Chain ◽  
Stimulating Factor

Abstract The common β chain (βc) of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 receptors is the major signaling subunit of these receptors coupling ligand binding to multiple biological activities. It is thought that these multiple functions arise as a consequence of the recruitment of specific signaling molecules to tyrosine-phosphorylated residues in the cytoplasmic domain of βc. However, the contribution of serine phosphorylation in βc to the recruitment of signaling molecules is not known. We show here the identification of a phosphoserine motif in the cytoplasmic domain of βc that interacts with the adaptor protein 14-3-3ζ. Coimmunoprecipitation and pull-down experiments with a glutathione S-transferase (GST):14-3-3ζ fusion protein showed that 14-3-3 directly associates with βc but not the GM-CSF receptor  chain. C-terminal truncation mutants of βcfurther showed that a region between amino acids 544 and 626 in βc was required for its association with 14-3-3ζ. This region contains the sequence 582HSRSLP587, which closely resembles the RSXSXP (where S is phosphorylated) consensus 14-3-3 binding site identified in a number of signaling molecules, including Raf-1. Significantly, substitution of582HSRSLP587 for EFAAAA completely abolished interaction of βc with GST–14-3-3ζ. Furthermore, the interaction of βc with GST–14-3-3 was greatly reduced in the presence of a peptide containing the 14-3-3 binding site, but only when 585Ser was phosphorylated. Direct binding experiments showed that the peptide containing phosphorylated 585Ser bound 14-3-3ζ with an affinity of 150 nmol/L. To study the regulation of 585S phosphorylation in vivo, we raised antibodies that specifically recognized 585Ser-phosphorylated βc. Using these antibodies, we showed that GM-CSF stimulation strongly upregulated 585Ser phosphorylation in M1 myeloid leukemic cells. The proximity of the SHC-binding site (577Tyr) to the 14-3-3–binding site (582HSRSLP587) and their conservation between mouse, rat, and human βc but not in other cytokine receptors suggest that they form a distinct motif that may subserve specialized functions associated with the GM-CSF, IL-3, and IL-5 receptors.

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