scholarly journals Single Cell Transcriptomics of Ependymal Cells Across Age, Region and Species Reveals Cilia-Related and Metal Ion Regulatory Roles as Major Conserved Ependymal Cell Functions

2021 ◽  
Vol 15 ◽  
Author(s):  
Adam MacDonald ◽  
Brianna Lu ◽  
Maxime Caron ◽  
Nina Caporicci-Dinucci ◽  
Dale Hatrock ◽  
...  
Keyword(s):  
Single Cell ◽  
Spinal Canal ◽  
Metal Ion ◽  
Ependymal Cell ◽  
Critical Role ◽  
Ependymal Cells ◽  
Cellular Transport ◽  
Cell Functions ◽  
Metal Ion Homeostasis ◽  
The Brain

Ependymal cells are ciliated-epithelial glial cells that develop from radial glia along the surface of the ventricles of the brain and the spinal canal. They play a critical role in cerebrospinal fluid (CSF) homeostasis, brain metabolism, and the clearance of waste from the brain. These cells have been implicated in disease across the lifespan including developmental disorders, cancer, and neurodegenerative disease. Despite this, ependymal cells remain largely understudied. Using single-cell RNA sequencing data extracted from publicly available datasets, we make key findings regarding the remarkable conservation of ependymal cell gene signatures across age, region, and species. Through this unbiased analysis, we have discovered that one of the most overrepresented ependymal cell functions that we observed relates to a critically understudied role in metal ion homeostasis. Our analysis also revealed distinct subtypes and states of ependymal cells across regions and ages of the nervous system. For example, neonatal ependymal cells maintained a gene signature consistent with developmental processes such as determination of left/right symmetry; while adult ventricular ependymal cells, not spinal canal ependymal cells, appeared to express genes involved in regulating cellular transport and inflammation. Together, these findings highlight underappreciated functions of ependymal cells, which will be important to investigate in order to better understand these cells in health and disease.

scholarly journals Streptococcus pneumoniae-Induced Inhibition of Rat Ependymal Cilia Is Attenuated by Antipneumolysin Antibody

2004 ◽  
Vol 72 (11) ◽  
pp. 6694-6698 ◽  
Author(s):  
Robert A. Hirst ◽  
Bashir J. Mohammed ◽  
Timothy J. Mitchell ◽  
Peter W. Andrew ◽  
Christopher O'Callaghan
Keyword(s):  
Streptococcus Pneumoniae ◽  
Therapeutic Potential ◽  
Ependymal Cell ◽  
Ex Vivo ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Ependymal Cells ◽  
Wild Type ◽  
Ependymal Cilia ◽  
The Brain

ABSTRACT Ciliated ependymal cells line the ventricular surfaces and aqueducts of the brain. In ex vivo experiments, pneumolysin caused rapid inhibition of the ependymal ciliary beat frequency and caused ependymal cell disruption. Wild-type pneumococci and pneumococci deficient in pneumolysin caused ciliary slowing, but penicillin lysis of wild-type, not pneumolysin-deficient, pneumococci increased the extent of ciliary inhibition. This effect was abolished by antipneumolysin antibody. Ependymal ciliary stasis by purified pneumolysin was also blocked by the addition of antipneumolysin monoclonal antibodies. These data show that antibiotic lysis of Streptococcus pneumoniae can be detrimental to the ciliated ependyma and that antipneumolysin antibody may have a therapeutic potential.

scholarly journals Characterising the brain metalloproteome in Down syndrome patients with concomitant Alzheimer's pathology

Metallomics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 114-132
Author(s):  
Nakisa Malakooti ◽  
Blaine Roberts ◽  
Melanie A. Pritchard ◽  
Irene Volitakis ◽  
Ron C. Kim ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Characteristic Feature ◽  
Metal Ion ◽  
Ion Homeostasis ◽  
Metal Ion Homeostasis ◽  
Down Syndrome Brain ◽  
Alzheimer’S Pathology ◽  
The Brain

A failure in metal ion homeostasis may be a characteristic feature of the Down syndrome brain.

scholarly journals Id4 is required for normal ependymal cell development

2021 ◽  
Author(s):  
Brenda Rocamonde ◽  
Vicente Herranz-Pérez ◽  
Jose-Manuel Garcia-Verdugo ◽  
Emmanuelle Huillard
Keyword(s):  
Radial Glia ◽  
Ependymal Cell ◽  
Cell Number ◽  
Cell Development ◽  
Ependymal Cells ◽  
Cerebrospinal Fluid Flow ◽  
Multiciliated Cells ◽  
Brain And Spinal Cord ◽  
The Brain

AbstractEpendymal cells are radial glia-derived multiciliated cells lining the lateral ventricles of the brain and spinal cord. Correct development and coordinated cilia beating is essential for proper cerebrospinal fluid flow (CSF) and neurogenesis modulation. Dysfunctions of ependymal cells were associated with transcription factor deregulation. Here we provide evidence that the transcriptional regulator Id4 is involved in ependymal cell development and maturation. We observed that Id4-deficient mice display altered ependymal cytoarchitecture, decreased ependymal cell number, altered CSF flow and enlarged ventricles. Our findings open the way for a potential role of Id4 in ependymal cell development and/or motor cilia function.

scholarly journals ID4 Is Required for Normal Ependymal Cell Development

2021 ◽  
Vol 15 ◽  
Author(s):  
Brenda Rocamonde ◽  
Vicente Herranz-Pérez ◽  
Jose Manuel Garcia-Verdugo ◽  
Emmanuelle Huillard
Keyword(s):  
Radial Glia ◽  
Ependymal Cell ◽  
Cell Number ◽  
Cell Development ◽  
Ependymal Cells ◽  
Multiciliated Cells ◽  
Delayed Maturation ◽  
Brain And Spinal Cord ◽  
The Brain

Ependymal cells are radial glia-derived multiciliated cells lining the lateral ventricles of the brain and spinal cord. Correct development and coordinated cilia beating is essential for proper cerebrospinal fluid (CSF) flow and neurogenesis modulation. Dysfunctions of ependymal cells were associated with transcription factor deregulation. Here we provide evidence that the transcriptional regulator ID4 is involved in ependymal cell development and maturation. We observed that Id4-deficient mice display altered ventricular cell cytoarchitecture, decreased ependymal cell number and enlarged ventricles. In addition, absence of ID4 during embryonic development resulted in decreased ependymal cell number and delayed maturation. Our findings open the way for a potential role of ID4 in ependymal cell development and motor cilia function.

scholarly journals Recent Developments in Metal-Based Drugs and Chelating Agents for Neurodegenerative Diseases Treatments

2019 ◽  
Vol 20 (8) ◽  
pp. 1829 ◽  
Author(s):  
Sales ◽  
Prandi ◽  
Castro ◽  
Leal ◽  
Cunha ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Metal Ion ◽  
Chelating Agents ◽  
Ion Homeostasis ◽  
Disruptive Disorders ◽  
Metal Ion Homeostasis ◽  
Wide Range ◽  
Recent Developments ◽  
Specific Proteins ◽  
The Brain

The brain has a unique biological complexity and is responsible for important functions in the human body, such as the command of cognitive and motor functions. Disruptive disorders that affect this organ, e.g. neurodegenerative diseases (NDDs), can lead to permanent damage, impairing the patients’ quality of life and even causing death. In spite of their clinical diversity, these NDDs share common characteristics, such as the accumulation of specific proteins in the cells, the compromise of the metal ion homeostasis in the brain, among others. Despite considerable advances in understanding the mechanisms of these diseases and advances in the development of treatments, these disorders remain uncured. Considering the diversity of mechanisms that act in NDDs, a wide range of compounds have been developed to act by different means. Thus, promising compounds with contrasting properties, such as chelating agents and metal-based drugs have been proposed to act on different molecular targets as well as to contribute to the same goal, which is the treatment of NDDs. This review seeks to discuss the different roles and recent developments of metal-based drugs, such as metal complexes and metal chelating agents as a proposal for the treatment of NDDs.

scholarly journals Mutant Cx30-A88V mice exhibit hydrocephaly and sex-dependent behavioral abnormalities, implicating a functional role for Cx30 in the brain

2021 ◽  
Vol 14 (1) ◽  
pp. dmm046235
Author(s):  
Nicole M. Novielli-Kuntz ◽  
Eric R. Press ◽  
Kevin Barr ◽  
Marco A. M. Prado ◽  
Dale W. Laird
Keyword(s):  
Connexin 43 ◽  
Cell Layer ◽  
Ependymal Cell ◽  
Morphological Changes ◽  
Abnormal Behavior ◽  
Brain Morphology ◽  
Ependymal Cells ◽  
Male And Female ◽  
Female Mice ◽  
The Brain

ABSTRACTConnexin 30 (Cx30; also known as Gjb6 when referring to the mouse gene) is expressed in ependymal cells of the brain ventricles, in leptomeningeal cells and in astrocytes rich in connexin 43 (Cx43), leading us to question whether patients harboring GJB6 mutations exhibit any brain anomalies. Here, we used mice harboring the human disease-associated A88V Cx30 mutation to address this gap in knowledge. Brain Cx30 levels were lower in male and female Cx30A88V/A88V mice compared with Cx30A88V/+ and Cx30+/+ mice, whereas Cx43 levels were lower only in female Cx30 mutant mice. Characterization of brain morphology revealed a disrupted ependymal cell layer, significant hydrocephalus and enlarged ventricles in 3- to 6-month-old adult male and female Cx30A88V/A88V mice compared with Cx30A88V/+ or Cx30+/+ sex-matched littermate mice. To determine the functional significance of these molecular and morphological changes, we investigated a number of behavioral activities in these mice. Interestingly, only female Cx30A88V/A88V mice exhibited abnormal behavior compared with all other groups. Cx30A88V/A88V female mice demonstrated increased locomotor and exploratory activity in both the open field and the elevated plus maze. They also exhibited dramatically reduced ability to learn the location of the escape platform during Morris water maze training, although they were able to swim as well as other genotypes. Our findings suggest that the homozygous A88V mutation in Cx30 causes major morphological changes in the brain of aging mice, possibly attributable to an abnormal ependymal cell layer. Remarkably, these changes had a more pronounced consequence for cognitive function in female mice, which is likely to be linked to the dysregulation of both Cx30 and Cx43 levels in the brain.

scholarly journals Microglia activated by microbial neuraminidase contributes to ependymal cell death

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
María del Mar Fernández-Arjona ◽  
Ana León-Rodríguez ◽  
María Dolores López-Ávalos ◽  
Jesús M. Grondona
Keyword(s):  
Cell Death ◽  
Ependymal Cell ◽  
Constitutive Expression ◽  
Ependymal Cells ◽  
Ventricular Wall ◽  
Blocking Antibody ◽  
Activated Microglia ◽  
Functional Blocking ◽  
Blocking Antibodies ◽  
The Brain

AbstractThe administration of microbial neuraminidase into the brain ventricular cavities of rodents represents a model of acute aseptic neuroinflammation. Ependymal cell death and hydrocephalus are unique features of this model. Here we demonstrate that activated microglia participates in ependymal cell death. Co-cultures of pure microglia with ependymal cells (both obtained from rats) were performed, and neuraminidase or lipopolysaccharide were used to activate microglia. Ependymal cell viability was unaltered in the absence of microglia or inflammatory stimulus (neuraminidase or lipopolysaccharide). The constitutive expression by ependymal cells of receptors for cytokines released by activated microglia, such as IL-1β, was demonstrated by qPCR. Besides, neuraminidase induced the overexpression of both receptors in ventricular wall explants. Finally, ependymal viability was evaluated in the presence of functional blocking antibodies against IL-1β and TNFα. In the co-culture setting, an IL-1β blocking antibody prevented ependymal cell death, while TNFα antibody did not. These results suggest that activated microglia are involved in the ependymal damage that occurs after the administration of neuraminidase in the ventricular cavities, and points to IL-1β as possible mediator of such effect. The relevance of these results lies in the fact that brain infections caused by neuraminidase-bearing pathogens are frequently associated to ependymal death and hydrocephalus.

Metabolic Regulation and Related Molecular Mechanisms in Various Stem Cell Functions

2020 ◽  
Vol 15 (6) ◽  
pp. 531-546 ◽  
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Oxidative Phosphorylation ◽  
Metabolic Pathways ◽  
Critical Role ◽  
The Self ◽  
Specific Cell ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Cell Functions

Recent studies on the mechanisms that link metabolic changes with stem cell fate have deepened our understanding of how specific metabolic pathways can regulate various stem cell functions during the development of an organism. Although it was originally thought to be merely a consequence of the specific cell state, metabolism is currently known to play a critical role in regulating the self-renewal capacity, differentiation potential, and quiescence of stem cells. Many studies in recent years have revealed that metabolic pathways regulate various stem cell behaviors (e.g., selfrenewal, migration, and differentiation) by modulating energy production through glycolysis or oxidative phosphorylation and by regulating the generation of metabolites, which can modulate multiple signaling pathways. Therefore, a more comprehensive understanding of stem cell metabolism could allow us to establish optimal culture conditions and differentiation methods that would increase stem cell expansion and function for cell-based therapies. However, little is known about how metabolic pathways regulate various stem cell functions. In this context, we review the current advances in metabolic research that have revealed functional roles for mitochondrial oxidative phosphorylation, anaerobic glycolysis, and oxidative stress during the self-renewal, differentiation and aging of various adult stem cell types. These approaches could provide novel strategies for the development of metabolic or pharmacological therapies to promote the regenerative potential of stem cells and subsequently promote their therapeutic utility.

scholarly journals Signaling pathways in intestinal homeostasis and colorectal cancer: KRAS at centre stage

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Camille Ternet ◽  
Christina Kiel
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathways ◽  
Intestinal Microbiota ◽  
Critical Role ◽  
Neuroendocrine Cells ◽  
Cell Junction ◽  
Intestinal Cell ◽  
Intestinal Homeostasis ◽  
Cell Functions ◽  
The Impact

AbstractThe intestinal epithelium acts as a physical barrier that separates the intestinal microbiota from the host and is critical for preserving intestinal homeostasis. The barrier is formed by tightly linked intestinal epithelial cells (IECs) (i.e. enterocytes, goblet cells, neuroendocrine cells, tuft cells, Paneth cells, and M cells), which constantly self-renew and shed. IECs also communicate with microbiota, coordinate innate and adaptive effector cell functions. In this review, we summarize the signaling pathways contributing to intestinal cell fates and homeostasis functions. We focus especially on intestinal stem cell proliferation, cell junction formation, remodelling, hypoxia, the impact of intestinal microbiota, the immune system, inflammation, and metabolism. Recognizing the critical role of KRAS mutants in colorectal cancer, we highlight the connections of KRAS signaling pathways in coordinating these functions. Furthermore, we review the impact of KRAS colorectal cancer mutants on pathway rewiring associated with disruption and dysfunction of the normal intestinal homeostasis. Given that KRAS is still considered undruggable and the development of treatments that directly target KRAS are unlikely, we discuss the suitability of targeting pathways downstream of KRAS as well as alterations of cell extrinsic/microenvironmental factors as possible targets for modulating signaling pathways in colorectal cancer.

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