scholarly journals Interlaminar Glia and Other Glial Themes Revisited: Pending Answers Following Three Decades of Glial Research

Neuroglia ◽  
2018 ◽  
Vol 1 (1) ◽  
pp. 7-20 ◽  
Author(s):  
Jorge Colombo
Keyword(s):  
Glial Cell ◽  
Cell Biology ◽  
Factors Affecting ◽  
Primate Brain ◽  
Glial Function ◽  
And Function ◽  
Main Model ◽  
Careful Assessment ◽  
Human Primate

This review aims to highlight the various significant matters in glial research stemming from personal work by the author and associates at the Unit of Applied Neurobiology (UNA, CEMIC-CONICET), and some of the pending questions. A reassessment and further comments on interlaminar astrocytes—an astroglial cell type that is specific to humans and other non-human primates, and is not found in rodents, is presented. Tentative hypothesis regarding their function and future possible research lines that could contribute to further the analysis of their development and possible role(s), are suggested. The possibility that they function as a separate entity from the “territorial” astrocytes, is also considered. In addition, the potential significance of our observations on interspecies differences in in vitro glial cell dye coupling, on glial diffusible factors affecting the induction of this glial phenotype, and on their interference with the cellular toxic effects of cerebrospinal fluid obtained from l-DOPA treated patients with Parkinson´s disease, is also considered. The major differences oberved in the cerebral cortex glial layout between human and rodents—the main model for studying glial function and pathology—calls for a careful assessment of known and potential species differences in all aspects of glial cell biology. This is essential to provide a better understanding of the organization and function of human and non-human primate brain, and of the neurobiological basis of their behavior.

scholarly journals Membrane-associated phase separation: organization and function emerge from a two-dimensional milieu

2021 ◽  
Author(s):  
Jonathon A Ditlev
Keyword(s):  
Phase Separation ◽  
Cell Biology ◽  
Cellular Environment ◽  
Condensate Formation ◽  
Associated Proteins ◽  
Available Technology ◽  
And Function ◽  
Surrounding Membrane

Abstract Liquid‒liquid phase separation (LLPS) of biomolecules has emerged as an important mechanism that contributes to cellular organization. Phase separated biomolecular condensates, or membrane-less organelles, are compartments composed of specific biomolecules without a surrounding membrane in the nucleus and cytoplasm. LLPS also occurs at membranes, where both lipids and membrane-associated proteins can de-mix to form phase separated compartments. Investigation of these membrane-associated condensates using in vitro biochemical reconstitution and cell biology has provided key insights into the role of phase separation in membrane domain formation and function. However, these studies have generally been limited by available technology to study LLPS on model membranes and the complex cellular environment that regulates condensate formation, composition, and function. Here, I briefly review our current understanding of membrane-associated condensates, establish why LLPS can be advantageous for certain membrane-associated condensates, and offer a perspective for how these condensates may be studied in the future.

scholarly journals Developments and Opportunities for 3D Bioprinted Organoids

2021 ◽  
Vol 7 (3) ◽  
pp. 364
Author(s):  
Ya Ren ◽  
Xue Yang ◽  
Zhengjiang Ma ◽  
Xin Sun ◽  
Yuxin Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Biology ◽  
Adult Stem Cells ◽  
Materials Science ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Key Characteristics ◽  
And Function ◽  
Further Development

Organoids developed from pluripotent stem cells or adult stem cells are three-dimensional cell cultures possessing certain key characteristics of their organ counterparts, and they can mimic certain biological developmental processes of organs in vitro. Therefore, they have promising applications in drug screening, disease modeling, and regenerative repair of tissues and organs. However, the construction of organoids currently faces numerous challenges, such as breakthroughs in scale size, vascularization, better reproducibility, and precise architecture in time and space. Recently, the application of bioprinting has accelerated the process of organoid construction. In this review, we present current bioprinting techniques and the application of bioinks and summarize examples of successful organoid bioprinting. In the future, a multidisciplinary combination of developmental biology, disease pathology, cell biology, and materials science will aid in overcoming the obstacles pertaining to the bioprinting of organoids. The combination of bioprinting and organoids with a focus on structure and function can facilitate further development of real organs.

scholarly journals Cell-type-specific promoters for C. elegans glia

2020 ◽  
Author(s):  
Wendy Fung ◽  
Leigh Wexler ◽  
Maxwell G. Heiman
Keyword(s):  
Glial Cell ◽  
Internal State ◽  
Cell Types ◽  
Cell Type ◽  
Sequencing Data ◽  
C Elegans ◽  
External Conditions ◽  
Glial Function ◽  
Cell Type Specific ◽  
And Function

ABSTRACTGlia shape the development and function of the C. elegans nervous system, especially its sense organs and central neuropil (nerve ring). Cell-type-specific promoters allow investigators to label or manipulate individual glial cell types, and therefore provide a key tool for deciphering glial function. In this technical resource, we compare the specificity, brightness, and consistency of cell-type-specific promoters for C. elegans glia. We identify a set of promoters for the study of seven glial cell types (F16F9.3, amphid and phasmid sheath glia; F11C7.2, amphid sheath glia only; grl-2, amphid and phasmid socket glia; hlh-17, cephalic (CEP) sheath glia; and grl-18, inner labial (IL) socket glia) as well as a pan-glial promoter (mir-228). We compare these promoters to promoters that are expressed more variably in combinations of glial cell types (delm-1 and itx-1). We note that the expression of some promoters depends on external conditions or the internal state of the organism, such as developmental stage, suggesting glial plasticity. Finally, we demonstrate an approach for prospectively identifying cell-type-specific glial promoters using existing single-cell sequencing data, and we use this approach to identify two novel promoters specific to IL socket glia (col-53 and col-177).

scholarly journals Targeting neuronal and glial cell types with synthetic promoter AAVs in mice, non-human primates, and humans

2018 ◽  
Author(s):  
Josephine Jüttner ◽  
Arnold Szabo ◽  
Brigitte Gross-Scherf ◽  
Rei K. Morikawa ◽  
Santiago B. Rompani ◽  
...  
Keyword(s):  
Glial Cell ◽  
Viral Vectors ◽  
Cell Types ◽  
Mouse Retina ◽  
Specific Cell ◽  
Synthetic Promoter ◽  
Brain Circuits ◽  
Human Primate

SummaryTargeting genes to specific neuronal or glial cell types is valuable both for understanding and for repairing brain circuits. Adeno-associated viral vectors (AAVs) are frequently used for gene delivery, but targeting expression to specific cell types is a challenge. We created a library of 230 AAVs, each with a different synthetic promoter designed using four independent strategies. We show that ~11% of these AAVs specifically target expression to neuronal and glial cell types in the mouse retina, mouse brain, non-human primate retinain vivo, and in the human retinain vitro. We demonstrate applications for recording, stimulation, and molecular characterization, as well as the intersectional and combinatorial labeling of cell types. These resources and approaches allow economic, fast, and efficient cell-type targeting in a variety of species, both for fundamental science and for gene therapy.

scholarly journals Brain/MINDS: brain-mapping project in Japan

2015 ◽  
Vol 370 (1668) ◽  
pp. 20140310 ◽  
Author(s):  
Hideyuki Okano ◽  
Atsushi Miyawaki ◽  
Kiyoto Kasai
Keyword(s):  
Human Brain ◽  
Brain Mapping ◽  
Common Marmoset ◽  
Neuronal Circuits ◽  
Primate Brain ◽  
Major Subject ◽  
The Usa ◽  
Subject Areas ◽  
And Function ◽  
Human Primate

There is an emerging interest in brain-mapping projects in countries across the world, including the USA, Europe, Australia and China. In 2014, Japan started a brain-mapping project called Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS). Brain/MINDS aims to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain, and takes advantage of a unique non-human primate animal model, the common marmoset ( Callithrix jacchus ). In Brain/MINDS, the RIKEN Brain Science Institute acts as a central institute. The objectives of Brain/MINDS can be categorized into the following three major subject areas: (i) structure and functional mapping of a non-human primate brain (the marmoset brain); (ii) development of innovative neurotechnologies for brain mapping; and (iii) human brain mapping; and clinical research. Brain/MINDS researchers are highly motivated to identify the neuronal circuits responsible for the phenotype of neurological and psychiatric disorders, and to understand the development of these devastating disorders through the integration of these three subject areas.

scholarly journals BrainPhys neuronal medium optimized for imaging and optogenetics in vitro

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Michael Zabolocki ◽  
Kasandra McCormack ◽  
Mark van den Hurk ◽  
Bridget Milky ◽  
Andrew P. Shoubridge ◽  
...  
Keyword(s):  
Cell Biology ◽  
Culture Conditions ◽  
Cellular Reprogramming ◽  
Synaptic Activity ◽  
Neuronal Cultures ◽  
Neuronal Viability ◽  
Human Neurons ◽  
Wide Range ◽  
And Function

AbstractThe capabilities of imaging technologies, fluorescent sensors, and optogenetics tools for cell biology are advancing. In parallel, cellular reprogramming and organoid engineering are expanding the use of human neuronal models in vitro. This creates an increasing need for tissue culture conditions better adapted to live-cell imaging. Here, we identify multiple caveats of traditional media when used for live imaging and functional assays on neuronal cultures (i.e., suboptimal fluorescence signals, phototoxicity, and unphysiological neuronal activity). To overcome these issues, we develop a neuromedium called BrainPhys™ Imaging (BPI) in which we optimize the concentrations of fluorescent and phototoxic compounds. BPI is based on the formulation of the original BrainPhys medium. We benchmark available neuronal media and show that BPI enhances fluorescence signals, reduces phototoxicity and optimally supports the electrical and synaptic activity of neurons in culture. We also show the superior capacity of BPI for optogenetics and calcium imaging of human neurons. Altogether, our study shows that BPI improves the quality of a wide range of fluorescence imaging applications with live neurons in vitro while supporting optimal neuronal viability and function.

scholarly journals Vascular lung triculture organoid via soluble extracellular matrix suspension

2021 ◽  
Author(s):  
Jonard Corpuz Valdoz ◽  
Nicholas A Franks ◽  
Collin G Cribbs ◽  
Dallin J Jacobs ◽  
Ethan L Dodson ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Biology ◽  
Disease Modeling ◽  
3D Culture ◽  
Culture Method ◽  
Matrix Proteins ◽  
Dependent Relationship ◽  
Shaped Cell ◽  
And Function

Scaffold-free tissue engineering is desired in creating consistently sized and shaped cell aggregates but has been limited to spheroid-like structure and function, thus restricting its use in accurate disease modeling. Here, we show formation of a viable lung organoid from epithelial, endothelial, and fibroblast stable cell lines in suspension culture supplemented with soluble concentrations of extracellular matrix proteins (ECM). We demonstrate the importance of soluble ECM in organotypic patterning with the emergence of air space-like gas exchange units, formation of branching, perfusable vasculature, and increased 3D growth. Our results show a dependent relationship between enhanced fibronectin fibril assembly and the incorporation of ECM in the organoid. Endothelial branching was found to depend on both soluble ECM and fibroblast. We successfully applied this technology in modeling lung fibrosis via bleomycin induction and test a potential antifibrotic drug in vitro while maintaining fundamental cell-cell interactions in lung tissue. Our human fluorescent lung organoid (hFLO) model accurately represents features of pulmonary fibrosis which were ameliorated by fasudil treatment. We demonstrate a 3D culture method with potential of creating organoids from mature cells, thus opening avenues for disease modeling and regenerative medicine, enhancing understanding of lung cell biology in health and lung disease.

scholarly journals BRCA1-Dependent Ubiquitination of γ-Tubulin Regulates Centrosome Number

2004 ◽  
Vol 24 (19) ◽  
pp. 8457-8466 ◽  
Author(s):  
Lea M. Starita ◽  
Yuka Machida ◽  
Satish Sankaran ◽  
Joshua E. Elias ◽  
Karen Griffin ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cell Biology ◽  
Chromosomal Instability ◽  
Mammary Tissue ◽  
Biological Impact ◽  
Binding Partner ◽  
Mammary Cell ◽  
Rapid Amplification ◽  
And Function

ABSTRACT Proper centrosome duplication and spindle formation are crucial for prevention of chromosomal instability, and BRCA1 plays a role in this process. In this study, transient inhibition of BRCA1 function in cell lines derived from mammary tissue caused rapid amplification and fragmentation of centrosomes. Cell lines tested that were derived from nonmammary tissues did not amplify the centrosome number in this transient assay. We tested whether BRCA1 and its binding partner, BARD1, ubiquitinate centrosome proteins. Results showed that centrosome components, including γ-tubulin, are ubiquitinated by BRCA1/BARD1 in vitro. The in vitro ubiquitination of γ-tubulin was specific, and function of the carboxy terminus was necessary for this reaction; truncated BRCA1 did not ubiquitinate γ-tubulin. BRCA1/BARD1 ubiquitinated lysines 48 and 344 of γ-tubulin in vitro, and expression in cells of γ-tubulin K48R caused a marked amplification of centrosomes. This result supports the notion that the modification of these lysines in living cells is critical in the maintenance of centrosome number. One of the key problems in understanding the biology of BRCA1 has been the identification of a specific target of BRCA1/BARD1 ubiquitination and its effect on mammary cell biology. The results of this study identify a ubiquitination target and suggest a biological impact important in the etiology of breast cancer.

The integrin α6β4 and the biology of carcinoma

1996 ◽  
Vol 74 (6) ◽  
pp. 811-821 ◽  
Author(s):  
Isaac Rabinovitz ◽  
Arthur M. Mercurio
Keyword(s):  
Basement Membrane ◽  
Tumor Progression ◽  
Cell Biology ◽  
Altered Expression ◽  
Laminin 5 ◽  
Functional Studies ◽  
Integrin Α6β4 ◽  
Α6β4 Integrin ◽  
And Function

The integrin family of adhesion receptors plays a major role in epithelial organization and function. Moreover, the altered expression and function of specific integrins most likely contributes significantly to carcinoma progression. The integrin α6β4, the focus of this review, is a receptor for several members of the laminin family and is preferentially expressed at the basal surface of most epithelia, where it contributes to basement membrane interactions. Mounting evidence suggests that the α6β4 integrin plays a key role in carcinoma cell biology. Several histopathological studies have established a correlation between α6β4 integrin expression and tumor progression. The importance of α6β4 expression in tumors is underscored by the findings that invading fronts of several carcinomas are enriched in the expression of α6β4 integrin ligands, such as laminin-1 and laminin-5. The participation of the α6β4 integrin in invasion is supported further by in vitro functional studies using carcinoma cells that have been transfected with the β4 cDNA. The mechanisms by which α6β4 contributes to tumor progression are probably related to its mechanical and signaling properties and are currently under intense study.Key words: integrins, laminin receptors, basement membrane, extracellular matrix, metastasis.

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