scholarly journals Histone Methylations Define Neural Stem/Progenitor Cell Subtypes in the Mouse Subventricular Zone

2019 ◽  
Vol 57 (2) ◽  
pp. 997-1008 ◽  
Author(s):  
Zhichao Zhang ◽  
Adeel Manaf ◽  
Yanjiao Li ◽  
Sonia Peña Perez ◽  
Rajikala Suganthan ◽  
...  
Keyword(s):  
Subventricular Zone ◽  
Progenitor Cell ◽  
Individual Cell ◽  
Histone H3 ◽  
Cell Types ◽  
Mammalian Brain ◽  
Neural Stem Progenitor Cells ◽  
Neurologic Function ◽  
Novel Strategy ◽  
The Brain

Abstract Neural stem/progenitor cells (NSPCs) persist in the mammalian brain throughout life and can be activated in response to the physiological and pathophysiological stimuli. Epigenetic reprogramming of NPSC represents a novel strategy for enhancing the intrinsic potential of the brain to regenerate after brain injury. Therefore, defining the epigenetic features of NSPCs is important for developing epigenetic therapies for targeted reprogramming of NSPCs to rescue neurologic function after injury. In this study, we aimed at defining different subtypes of NSPCs by individual histone methylations. We found the three histone marks, histone H3 lysine 4 trimethylation (H3K4me3), histone H3 lysine 27 trimethylation (H3K27me3), and histone H3 lysine 36 trimethylation (H3K36me3), to nicely and dynamically portray individual cell types during neurodevelopment. First, we found all three marks co-stained with NSPC marker SOX2 in mouse subventricular zone. Then, CD133, Id1, Mash1, and DCX immunostaining were used to define NSPC subtypes. Type E/B, B/C, and C/A cells showed high levels of H3K27me3, H3K36me3, and H3K4me3, respectively. Our results reveal defined histone methylations of NSPC subtypes supporting that epigenetic regulation is critical for neurogenesis and for maintaining NSPCs.

scholarly journals The Expanding Cell Diversity of the Brain Vasculature

2020 ◽  
Vol 11 ◽  
Author(s):  
Jayden M. Ross ◽  
Chang Kim ◽  
Denise Allen ◽  
Elizabeth E. Crouch ◽  
Kazim Narsinh ◽  
...  
Keyword(s):  
Regional Blood Flow ◽  
Cell Types ◽  
Brain Health ◽  
Vascular Cell ◽  
Brain Vasculature ◽  
Genomic Technologies ◽  
Cell Diversity ◽  
Cell Type Specific ◽  
Neurologic Function ◽  
The Brain

The cerebrovasculature is essential to brain health and is tasked with ensuring adequate delivery of oxygen and metabolic precursors to ensure normal neurologic function. This is coordinated through a dynamic, multi-directional cellular interplay between vascular, neuronal, and glial cells. Molecular exchanges across the blood–brain barrier or the close matching of regional blood flow with brain activation are not uniformly assigned to arteries, capillaries, and veins. Evidence has supported functional segmentation of the brain vasculature. This is achieved in part through morphologic or transcriptional heterogeneity of brain vascular cells—including endothelium, pericytes, and vascular smooth muscle. Advances with single cell genomic technologies have shown increasing cell complexity of the brain vasculature identifying previously unknown cell types and further subclassifying transcriptional diversity in cardinal vascular cell types. Cell-type specific molecular transitions or zonations have been identified. In this review, we summarize emerging evidence for the expanding vascular cell diversity in the brain and how this may provide a cellular basis for functional segmentation along the arterial-venous axis.

scholarly journals TAZ Represses the Neuronal Commitment of Neural Stem Cells

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2230
Author(s):  
Natalia Robledinos-Antón ◽  
Maribel Escoll ◽  
Kun-Liang Guan ◽  
Antonio Cuadrado
Keyword(s):  
Neuronal Differentiation ◽  
Subventricular Zone ◽  
Transcriptional Repression ◽  
Genetic Manipulation ◽  
Mammalian Brain ◽  
Additional Function ◽  
Neural Stem Progenitor Cells ◽  
Neuronal Lineage ◽  
Neuronal Commitment

The mechanisms involved in regulation of quiescence, proliferation, and reprogramming of Neural Stem Progenitor Cells (NSPCs) of the mammalian brain are still poorly defined. Here, we studied the role of the transcriptional co-factor TAZ, regulated by the WNT and Hippo pathways, in the homeostasis of NSPCs. We found that, in the murine neurogenic niches of the striatal subventricular zone and the dentate gyrus granular zone, TAZ is highly expressed in NSPCs and declines with ageing. Moreover, TAZ expression is lost in immature neurons of both neurogenic regions. To characterize mechanistically the role of TAZ in neuronal differentiation, we used the midbrain-derived NSPC line ReNcell VM to replicate in a non-animal model the factors influencing NSPC differentiation to the neuronal lineage. TAZ knock-down and forced expression in NSPCs led to increased and reduced neuronal differentiation, respectively. TEADs-knockdown indicated that these TAZ co-partners are required for the suppression of NSPCs commitment to neuronal differentiation. Genetic manipulation of the TAZ/TEAD system showed its participation in transcriptional repression of SOX2 and the proneuronal genes ASCL1, NEUROG2, and NEUROD1, leading to impediment of neurogenesis. TAZ is usually considered a transcriptional co-activator promoting stem cell proliferation, but our study indicates an additional function as a repressor of neuronal differentiation.

scholarly journals The Neurobiology of Selenium: Looking Back and to the Future

2021 ◽  
Vol 15 ◽  
Author(s):  
Ulrich Schweizer ◽  
Simon Bohleber ◽  
Wenchao Zhao ◽  
Noelia Fradejas-Villar
Keyword(s):  
Cell Biology ◽  
Molecular Mechanisms ◽  
Human Genetics ◽  
Epileptic Seizures ◽  
Cell Types ◽  
Mammalian Brain ◽  
The Individual ◽  
The Brain ◽  
Looking Back

Eighteen years ago, unexpected epileptic seizures in Selenop-knockout mice pointed to a potentially novel, possibly underestimated, and previously difficult to study role of selenium (Se) in the mammalian brain. This mouse model was the key to open the field of molecular mechanisms, i.e., to delineate the roles of selenium and individual selenoproteins in the brain, and answer specific questions like: how does Se enter the brain; which processes and which cell types are dependent on selenoproteins; and, what are the individual roles of selenoproteins in the brain? Many of these questions have been answered and much progress is being made to fill remaining gaps. Mouse and human genetics have together boosted the field tremendously, in addition to traditional biochemistry and cell biology. As always, new questions have become apparent or more pressing with solving older questions. We will briefly summarize what we know about selenoproteins in the human brain, glance over to the mouse as a useful model, and then discuss new questions and directions the field might take in the next 18 years.

scholarly journals Subependymal Zone: Immunohistochemically Distinct Compartment in the Adult Mammalian Forebrain

2004 ◽  
Vol 47 (4) ◽  
pp. 235-242 ◽  
Author(s):  
Jaroslav Mokrý ◽  
Dana Čížková ◽  
Jan Österreicher
Keyword(s):  
Cell Types ◽  
Brain Parenchyma ◽  
Mammalian Brain ◽  
Histological Structure ◽  
Astroglial Cell ◽  
Neuronal Markers ◽  
Subependymal Zone ◽  
Rat Forebrain ◽  
The Brain ◽  
Migratory Stream

The subependymal zone (SEZ) lining lateral walls of the lateral cerebral ventricles represents the site of active neurogenesis in the brain of adult mammals. Peroxidase immunohistochemistry performed in paraffin-embedded sections reveals that structural organization of the SEZ differs from other regions in the brain. The SEZ is devoid of synapses that are abundant in the adjacent striatal neuropil. Therefore immunostaining of synaptophysin detects sharp borders of the SEZ. Using immunophenotypization, we identified cell types constituting the SEZ in the intact rat forebrain. The presence of neural progenitor/stem cells was confirmed by finding of nestin-immunopositive cells. Detection of the astroglial marker GFAP confirmed that astrocytes represented major supporting elements responsible for creating a unique microenvironment of the SEZ. One type of the astroglia participated in covering surfaces of the blood vessels and boundaries of the SEZ. The second astroglial cell type formed branched elongated tubes that enwrapped other SEZ cell types with their cytoplasmic extensions. The interior of astrocytic channels was occupied with small densely aggregated NCAM-immunoreactive neuroblasts. Bipolar morphology indicated that these cells probably underwent migration. Immunodetection of other neuronal markers like β-III tubulin, MAP-2 and Pan neurofilaments identified positive cells in the neighbouring brain parenchyma but not in the SEZ. The rostral migratory stream (RMS) linked with the anterior SEZ had a similar structural arrangement. It contained a large amount of nestin+and vimentin+cells. The RMS consisted of GFAP+astrocytic tubes ensheathing NCAM+neuroblasts. On the contrary to the SEZ, the RMS neuroblasts expressed β-III tubulin. However, markers of postmitotic neurons MAP-2, Pan neurofilaments and synaptophysin were not expressed in the RMS. Our study describes a complex histological structure of the rat SEZ, identifies its individual cell types and demonstrates a usefulness of immunohistochemical detection of cell-specific markers in a study of microenvironment forming neurogenic zones in the mammalian brain.

Effects of Neuroinflammation on Neural Stem Cells

2016 ◽  
Vol 23 (1) ◽  
pp. 27-39 ◽  
Author(s):  
Ruxandra Covacu ◽  
Lou Brundin
Keyword(s):  
Immune Responses ◽  
Subventricular Zone ◽  
Neurological Diseases ◽  
Experimental Models ◽  
Adaptive Immune ◽  
Neural Stem Progenitor Cells ◽  
The Central Nervous System ◽  
And Migration ◽  
The Brain ◽  
Proliferation And Migration

Neural stem/progenitor cells (NSCs/NPCs) are present in different locations in the central nervous system. In the subgranular zone (SGZ) there is a constant generation of new neurons under normal conditions. New neurons are also formed from the subventricular zone (SVZ) NSCs, and they migrate anteriorly as neuroblast to the olfactory bulb in rodents, whereas in humans migration is directed toward striatum. Most CNS injuries elicit proliferation and migration of the NSCs toward the injury site, indicating the activation of a regenerative response. However, regeneration from NSC is incomplete, and this could be due to detrimental cues encountered during inflammation. Different CNS diseases and trauma cause activation of the innate and adaptive immune responses that influence the NSCs. Furthermore, NSCs in the brain react differently to inflammatory cues than their counterparts in the spinal cord. In this review, we have summarized the effects of inflammation on NSCs in relation to their origin and briefly described the NSC activity during different neurological diseases or experimental models.

scholarly journals Cloning of DNA corresponding to rare transcripts of rat brain: evidence of transcriptional and post-transcriptional control and of the existence of nonpolyadenylated transcripts.

1984 ◽  
Vol 4 (10) ◽  
pp. 2187-2197 ◽  
Author(s):  
M H Brilliant ◽  
N Sueoka ◽  
D M Chikaraishi
Keyword(s):  
Rat Brain ◽  
Transcriptional Control ◽  
Cultured Cells ◽  
Cell Clone ◽  
Cell Types ◽  
Mammalian Brain ◽  
Neural Cells ◽  
Genes Encoding ◽  
Liver And Kidney ◽  
The Brain

To examine the expression of genes encoding rare transcripts in the rat brain, we have characterized genomic DNA clones corresponding to this class. In brain cells, as in all cell types, rare transcripts constitute the majority of different sequences transcribed. Moreover, when compared with other tissues or cultured cells, brain tissue may be expected to have an even larger set of rare transcripts, some of which could be restricted to subpopulations of neural cells. We have identified seven clones whose transcripts are nonabundant, averaging less than three copies per cell. Clone rg13 (rat genomic 13) RNA was detected only in the brain, whereas RNA of a second clone, rg40, was also detected in the brain and in a melanoma. Transcripts of rg13 were found in cerebellum, cerebral cortex, and regions underlying the cortex, whereas rg40 transcripts were not detected in the cerebellum. Transcripts of both rg13 and rg40 were found in pelleted polysomal RNA. RNA of another clone, rg34, was found in the brain, liver, and kidney but was found in pelleted polysomal RNA only in the brain, suggesting that its expression may be post-transcriptionally controlled. The remaining four clones represent rare transcripts that are common to the brain, liver, and kidney; rg18 RNA is restricted to the nucleus, whereas rg3, rg26, and rg36 transcripts are found in the cytoplasm of all three tissues. Transcripts of the brain-specific clone, rg13, and the commonly expressed clone, rg3, are nonpolyadenylated, presumably belonging to the high-complexity, nonpolyadenylated class of transcripts in the mammalian brain.

scholarly journals Development of the entorhinal cortex occurs via parallel lamination during neurogenesis

2021 ◽  
Author(s):  
Yong Liu ◽  
Tobias Bergmann ◽  
Yuki Mori ◽  
Juan Miguel Peralvo Vidal ◽  
Maria Pihl ◽  
...  
Keyword(s):  
Entorhinal Cortex ◽  
Subventricular Zone ◽  
Deep Layer ◽  
Cell Types ◽  
Second Trimester ◽  
Gestational Length ◽  
Brdu Labeling ◽  
The Brain ◽  
Inside Out ◽  
Insight Into

AbstractThe entorhinal cortex (EC) is the spatial processing center of the brain and structurally is an interface between the three layered paleocortex and six layered neocortex, known as the periarchicortex. Limited studies indicate peculiarities in the formation of the EC such as early emergence of cells in layers (L) II and late deposition of LIII, as well as divergence in the timing of maturation of cell types in the superficial layers. In this study, we examine developmental events in the entorhinal cortex using an understudied model in neuroanatomy and development, the pig and supplement the research with BrdU labeling in the developing mouse EC. We determine the pig serves as an excellent anatomical model for studying human neurogenesis, given its long gestational length, presence of a moderate sized outer subventricular zone and early cessation of neurogenesis during gestation. Immunohistochemistry identified prominent clusters of OLIG2+ oligoprogenitor-like cells in the superficial layers of the lateral EC (LEC) that are sparser in the medial EC (MEC). These are first detected in the subplate during the early second semester. MRI analyses reveal an acceleration of EC growth at the end of the second trimester. BrdU labeling of the developing MEC, shows the deeper layers form first and prior to the superficial layers, but the LV/VI emerges in parallel and the LII/III emerges later, but also in parallel. We coin this lamination pattern parallel lamination. The early-born Reln+ stellate cells in the superficial layers express the classic LV marker, Bcl11b (Ctip2) and arise from a common progenitor that forms the late deep layer LV neurons. In summary, we characterize the developing EC in a novel animal model and outline in detail the formation of the EC. We further provide insight into how the periarchicortex forms in the brain, which differs remarkably to the inside-out lamination of the neocortex.

Cloning of DNA corresponding to rare transcripts of rat brain: evidence of transcriptional and post-transcriptional control and of the existence of nonpolyadenylated transcripts

1984 ◽  
Vol 4 (10) ◽  
pp. 2187-2197
Author(s):  
M H Brilliant ◽  
N Sueoka ◽  
D M Chikaraishi
Keyword(s):  
Rat Brain ◽  
Transcriptional Control ◽  
Cultured Cells ◽  
Cell Clone ◽  
Cell Types ◽  
Mammalian Brain ◽  
Neural Cells ◽  
Genes Encoding ◽  
Liver And Kidney ◽  
The Brain

To examine the expression of genes encoding rare transcripts in the rat brain, we have characterized genomic DNA clones corresponding to this class. In brain cells, as in all cell types, rare transcripts constitute the majority of different sequences transcribed. Moreover, when compared with other tissues or cultured cells, brain tissue may be expected to have an even larger set of rare transcripts, some of which could be restricted to subpopulations of neural cells. We have identified seven clones whose transcripts are nonabundant, averaging less than three copies per cell. Clone rg13 (rat genomic 13) RNA was detected only in the brain, whereas RNA of a second clone, rg40, was also detected in the brain and in a melanoma. Transcripts of rg13 were found in cerebellum, cerebral cortex, and regions underlying the cortex, whereas rg40 transcripts were not detected in the cerebellum. Transcripts of both rg13 and rg40 were found in pelleted polysomal RNA. RNA of another clone, rg34, was found in the brain, liver, and kidney but was found in pelleted polysomal RNA only in the brain, suggesting that its expression may be post-transcriptionally controlled. The remaining four clones represent rare transcripts that are common to the brain, liver, and kidney; rg18 RNA is restricted to the nucleus, whereas rg3, rg26, and rg36 transcripts are found in the cytoplasm of all three tissues. Transcripts of the brain-specific clone, rg13, and the commonly expressed clone, rg3, are nonpolyadenylated, presumably belonging to the high-complexity, nonpolyadenylated class of transcripts in the mammalian brain.

scholarly journals Regeneration and Plasticity in the Brain and Spinal Cord

2007 ◽  
Vol 27 (8) ◽  
pp. 1417-1430 ◽  
Author(s):  
Barbro B Johansson
Keyword(s):  
Spinal Cord ◽  
Progenitor Cells ◽  
Subventricular Zone ◽  
Cortical Neurons ◽  
Brain Plasticity ◽  
Brain Lesions ◽  
Mammalian Brain ◽  
Long Distance ◽  
Inhibitory Factors ◽  
The Brain

The concept of brain plasticity covers all the mechanisms involved in the capacity of the brain to adjust and remodel itself in response to environmental requirements, experience, skill acquisition, and new challenges including brain lesions. Advances in neuroimaging and neurophysiologic techniques have increased our knowledge of task-related changes in cortical representation areas in the intact and injured human brain. The recognition that neuronal progenitor cells proliferate and differentiate in the subventricular zone and dentate gyrus in the adult mammalian brain has raised the hope that regeneration may be possible after brain lesions. Regeneration will require that new cells differentiate, survive, and integrate into existing neural networks and that axons regenerate. To what extent this will be possible is difficult to predict. Current research explores the possibilities to modify endogenous neurogenesis and facilitate axonal regeneration using myelin inhibitory factors. After apoptotic damage in mice new cortical neurons can form long-distance connections. Progenitor cells from the subventricular zone migrate to cortical and subcortical regions after ischemic brain lesions, apparently directed by signals from the damaged region. Postmortem studies on human brains suggest that neurogenesis may be altered in degenerative diseases. Functional and anatomic data indicate that myelin inhibitory factors, cell implantation, and modification of extracellular matrix may be beneficial after spinal cord lesions. Neurophysiologic data demonstrating that new connections are functioning are needed to prove regeneration. Even if not achieving the goal, methods aimed at regeneration can be beneficial by enhancing plasticity in intact brain regions.

GLIAL-NEURONAL INTERACTIONS IN THE MAMMALIAN BRAIN

2002 ◽  
Vol 26 (4) ◽  
pp. 225-237 ◽  
Author(s):  
Glenn I. Hatton
Keyword(s):  
Morphological Changes ◽  
Cell Types ◽  
Mammalian Brain ◽  
Cell Type ◽  
Glia Cell ◽  
Functional Changes ◽  
Neuronal Interactions ◽  
System Functioning ◽  
Extracellular Microenvironment ◽  
The Brain

Recognition of the importance of glial cells in nervous system functioning is increasing, specifically regarding the modulation of neural activity. This brief review focuses on some of the morphological and functional interactions that take place between astroglia and neurons. Astrocyte-neuron interactions are of special interest because this glia cell type has intimate and dynamic associations with all parts of neurons, i.e., somata, dendrites, axons, and terminals. Activation of certain receptors on astrocytes produces morphological changes that result in new contacts between neurons, along with physiological and functional changes brought about by the new contacts. In response to activation of other receptors or changes in the extracellular microenvironment, astrocytes release neuroactive substances that directly excite or inhibit nearby neurons and may modulate synaptic transmission. Although some of these glial-neuronal interactions have been known for many years, others have been quite recently revealed, but together they are forming a compelling story of how these two major cell types in the brain carry out the complex tasks that mammalian nervous systems perform.

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