scholarly journals DAF-16/FoxO and DAF-12/VDR control cellular plasticity both cell-autonomously and via interorgan signaling

PLoS Biology ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. e3001204
Author(s):  
Ulkar Aghayeva ◽  
Abhishek Bhattacharya ◽  
Surojit Sural ◽  
Eliza Jaeger ◽  
Matthew Churgin ◽  
...  
Keyword(s):  
Nervous System ◽  
Tissue Remodeling ◽  
Cell Types ◽  
Nuclear Hormone Receptor ◽  
Specific Cell ◽  
Signaling Systems ◽  
Autonomous Function ◽  
Insulin Dependent ◽  
Adverse Environmental Conditions ◽  
Temporal Focus

Many cell types display the remarkable ability to alter their cellular phenotype in response to specific external or internal signals. Such phenotypic plasticity is apparent in the nematodeCaenorhabditis eleganswhen adverse environmental conditions trigger entry into the dauer diapause stage. This entry is accompanied by structural, molecular, and functional remodeling of a number of distinct tissue types of the animal, including its nervous system. The transcription factor (TF) effectors of 3 different hormonal signaling systems, the insulin-responsive DAF-16/FoxO TF, the TGFβ-responsive DAF-3/SMAD TF, and the steroid nuclear hormone receptor, DAF-12/VDR, a homolog of the vitamin D receptor (VDR), were previously shown to be required for entering the dauer arrest stage, but their cellular and temporal focus of action for the underlying cellular remodeling processes remained incompletely understood. Through the generation of conditional alleles that allowed us to spatially and temporally control gene activity, we show here that all 3 TFs are not only required to initiate tissue remodeling upon entry into the dauer stage, as shown before, but are also continuously required to maintain the remodeled state. We show that DAF-3/SMAD is required in sensory neurons to promote and then maintain animal-wide tissue remodeling events. In contrast, DAF-16/FoxO or DAF-12/VDR act cell-autonomously to control anatomical, molecular, and behavioral remodeling events in specific cell types. Intriguingly, we also uncover non-cell autonomous function of DAF-16/FoxO and DAF-12/VDR in nervous system remodeling, indicating the presence of several insulin-dependent interorgan signaling axes. Our findings provide novel perspectives into how hormonal systems control tissue remodeling.

scholarly journals DAF-16/FoxO and DAF-12/VDR control cellular plasticity both cell-autonomously and via interorgan signaling

2020 ◽  
Author(s):  
Ulkar Aghayeva ◽  
Abhishek Bhattacharya ◽  
Surojit Sural ◽  
Eliza Jaeger ◽  
Matt Churgin ◽  
...  
Keyword(s):  
Nervous System ◽  
Transcription Factor ◽  
Tissue Remodeling ◽  
Cell Types ◽  
Nuclear Hormone Receptor ◽  
Specific Cell ◽  
Signaling Systems ◽  
C Elegans ◽  
Insulin Dependent ◽  
Adverse Environmental Conditions

Many cell types display the remarkable ability to alter their cellular phenotype in response to specific external or internal signals. Such phenotypic plasticity is apparent in the nematode C. elegans when adverse environmental conditions trigger entry into the dauer diapause stage. This entry is accompanied by structural, molecular and functional remodeling of a number of distinct tissue types of the animal, including its nervous system. The transcription factor effectors of three different hormonal signaling systems, the insulin-responsive DAF-16/FoxO transcription factor, the TGFβ-responsive DAF-3/SMAD transcription factor and the steroid nuclear hormone receptor, DAF-12/VDR, a homolog of the vitamin D receptor, were previously shown to be required for entering the dauer arrest stage, but their cellular and temporal focus of action for the underlying cellular remodeling processes remained incompletely understood. Through the generation of conditional alleles that allowed us to spatially and temporally control gene activity, we show here that all three transcription factors are not only required to initiate tissue remodeling upon entry into the dauer stage, as shown before, but are also continuously required to maintain the remodeled state. We show that DAF-3/SMAD is required in sensory neurons to promote and then maintain animal-wide tissue remodeling events. In contrast, DAF-16/FoxO or DAF-12/VDR act cell autonomously to control anatomical, molecular and behavioral remodeling events in specific cell types. Intriguingly, we also uncover non-cell autonomous function of DAF-16/FoxO and DAF-12/VDR in nervous system remodeling, indicating the presence of several insulin-dependent inter-organ signaling axes. Our findings provide novel perspectives on how hormonal systems control tissue remodeling.

The role of globins in cardiovascular physiology

2021 ◽  
Author(s):  
T.C. Steven Keller ◽  
Christophe Lechauve ◽  
Alexander S Keller ◽  
Steven Brooks ◽  
Mitchell J Weiss ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Central Nervous System ◽  
Nervous System ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Specific Cell ◽  
In Cells

Globin proteins exist in every cell type of the vasculature, from erythrocytes to endothelial cells, vascular smooth muscle cells, and peripheral nerve cells. Many globin subtypes are also expressed in muscle tissues (including cardiac and skeletal muscle), in other organ-specific cell types, and in cells of the central nervous system. The ability of each of these globins to interact with molecular oxygen (O2) and nitric oxide (NO) is preserved across these contexts. Endothelial α-globin is an example of extra-erythrocytic globin expression. Other globins, including myoglobin, cytoglobin, and neuroglobin are observed in other vascular tissues. Myoglobin is observed primarily in skeletal muscle and smooth muscle cells surrounding the aorta or other large arteries. Cytoglobin is found in vascular smooth muscle but can also be expressed in non-vascular cell types, especially in oxidative stress conditions after ischemic insult. Neuroglobin was first observed in neuronal cells, and its expression appears to be restricted mainly to the central and peripheral nervous systems. Brain and central nervous system neurons expressing neuroglobin are positioned close to many arteries within the brain parenchyma and can control smooth muscle contraction and, thus, tissue perfusion and vascular reactivity. Overall, reactions between NO and globin heme-iron contribute to vascular homeostasis by regulating vasodilatory NO signals and scaveging reactive species in cells of the mammalian vascular system. Here, we discuss how globin proteins affect vascular physiology with a focus on NO biology, and offer perspectives for future study of these functions.

scholarly journals Localization of phosphotyrosine adaptor protein ShcD/SHC4 in the adult rat central nervous system

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Hannah N. Robeson ◽  
Hayley R. Lau ◽  
Laura A. New ◽  
Jasmin Lalonde ◽  
John N. Armstrong ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Olfactory Bulb ◽  
Adaptor Protein ◽  
Cell Types ◽  
Olfactory Nerve ◽  
Adult Brain ◽  
Specific Cell ◽  
Adult Rat ◽  
Fiber Tracts

Abstract Background Mammalian Shc (Src homology and collagen) proteins comprise a family of four phosphotyrosine adaptor molecules which exhibit varied spatiotemporal expression and signaling functions. ShcD is the most recently discovered homologue and it is highly expressed in the developing central nervous system (CNS) and adult brain. Presently however, its localization within specific cell types of mature neural structures has yet to be characterized. Results In the current study, we examine the expression profile of ShcD in the adult rat CNS using immunohistochemistry, and compare with those of the neuronally enriched ShcB and ShcC proteins. ShcD shows relatively widespread distribution in the adult brain and spinal cord, with prominent levels of staining throughout the olfactory bulb, as well as in sub-structures of the cerebellum and hippocampus, including the subgranular zone. Co-localization studies confirm the expression of ShcD in mature neurons and progenitor cells. ShcD immunoreactivity is primarily localized to axons and somata, consistent with the function of ShcD as a cytoplasmic adaptor. Regional differences in expression are observed among neural Shc proteins, with ShcC predominating in the hippocampus, cerebellum, and some fiber tracts. Interestingly, ShcD is uniquely expressed in the olfactory nerve layer and in glomeruli of the main olfactory bulb. Conclusions Together our findings suggest that ShcD may provide a distinct signaling contribution within the olfactory system, and that overlapping expression of ShcD with other Shc proteins may allow compensatory functions in the brain.

scholarly journals FIN-Seq: transcriptional profiling of specific cell types from frozen archived tissue of the human central nervous system

2019 ◽  
Author(s):  
Ryoji Amamoto ◽  
Emanuela Zuccaro ◽  
Nathan C Curry ◽  
Sonia Khurana ◽  
Hsu-Hsin Chen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Rna Sequencing ◽  
Human Tissue ◽  
Transcriptional Profiling ◽  
Cell Types ◽  
Specific Cell ◽  
Human Central Nervous System ◽  
Tissue Samples ◽  
Rna Profiling

Abstract Thousands of frozen, archived tissue samples from the human central nervous system (CNS) are currently available in brain banks. As recent developments in RNA sequencing technologies are beginning to elucidate the cellular diversity present within the human CNS, it is becoming clear that an understanding of this diversity would greatly benefit from deeper transcriptional analyses. Single cell and single nucleus RNA profiling provide one avenue to decipher this heterogeneity. An alternative, complementary approach is to profile isolated, pre-defined cell types and use methods that can be applied to many archived human tissue samples that have been stored long-term. Here, we developed FIN-Seq (Frozen Immunolabeled Nuclei Sequencing), a method that accomplishes these goals. FIN-Seq uses immunohistochemical isolation of nuclei of specific cell types from frozen human tissue, followed by bulk RNA-Sequencing. We applied this method to frozen postmortem samples of human cerebral cortex and retina and were able to identify transcripts, including low abundance transcripts, in specific cell types.

Abstract 3937: Generation and Analysis of Neural Crest- and Endothelial-specific Mutant Mice for Foxc1

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Seungwoon Seo ◽  
Hisaki Hayashi ◽  
Tsutomu Kume
Keyword(s):  
Neural Crest ◽  
Corneal Stroma ◽  
Cell Types ◽  
Mutant Mice ◽  
Specific Cell ◽  
Cardiovascular Development ◽  
Forkhead Transcription Factor ◽  
Vascular Abnormalities ◽  
Autonomous Function ◽  
Conditional Mutant

The forkhead transcription factor Foxc1 has been implicated in craniofacial, ocular and cardiovascular development. Foxc1 is expressed in mesoderm- and neural crest (NC)-derived cells, including endothelial cells (ECs) of the heart and blood vessels and vascular smooth muscle cells. However, the precise role of Foxc1 in specific cell types still remains unclear. Therefore, to define the distinct function of Foxc1 in NC and EC, we have generated conditional mutant mice for Foxc1 crossed with either Tie2-Cre or Wnt1-Cre mice. EC-specific Foxc1 mutants survive until adulthood with no apparent embryonic defects, although they show vascular abnormalities in the adult. By contrast, NC-specific Foxc1 mutants die perinately with haemorrhagic hydrocephalus, rudimentary frontal bones, and abnormal patterning of the aortic arch. NC-derived cells also give rise to the stroma and endothelium of the cornea, an avascular organ whose transparency is critical for vision. Importantly, we found that NC-specific Foxc1 mutants show failure of the formation of the anterior chamber and corneal endothelium in the eye. Mutant corneal stroma is much thicker than normal with increased cell proliferation. Most Intriguingly, NC-specific Foxc1 mutants exhibit ectopic neovascularization in the cornea with significant upregulation of Mmp9, sFlt1, Flt1 and Tek at E15.5, while Vegfa and Fgf expression is not changed. By contrast, the cornea of EC-specific Foxc1 mutants is normally formed and avascular. These data suggest that the cell-autonomous function of Foxc1 in the neural crest is essential for craniofacial and cardiovascular development and that Foxc1 plays an important role in inhibition of vascular formation in the cornea.

scholarly journals Building an RNA Sequencing Transcriptome of the Central Nervous System

2016 ◽  
Vol 22 (6) ◽  
pp. 579-592 ◽  
Author(s):  
Xiaomin Dong ◽  
Yanan You ◽  
Jia Qian Wu
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Rna Sequencing ◽  
Large Scale ◽  
Expression Profiles ◽  
Cell Types ◽  
Specific Cell ◽  
Rna Seq ◽  
The Central Nervous System

The composition and function of the central nervous system (CNS) is extremely complex. In addition to hundreds of subtypes of neurons, other cell types, including glia (astrocytes, oligodendrocytes, and microglia) and vascular cells (endothelial cells and pericytes) also play important roles in CNS function. Such heterogeneity makes the study of gene transcription in CNS challenging. Transcriptomic studies, namely the analyses of the expression levels and structures of all genes, are essential for interpreting the functional elements and understanding the molecular constituents of the CNS. Microarray has been a predominant method for large-scale gene expression profiling in the past. However, RNA-sequencing (RNA-Seq) technology developed in recent years has many advantages over microarrays, and has enabled building more quantitative, accurate, and comprehensive transcriptomes of the CNS and other systems. The discovery of novel genes, diverse alternative splicing events, and noncoding RNAs has remarkably expanded the complexity of gene expression profiles and will help us to understand intricate neural circuits. Here, we discuss the procedures and advantages of RNA-Seq technology in mammalian CNS transcriptome construction, and review the approaches of sample collection as well as recent progress in building RNA-Seq-based transcriptomes from tissue samples and specific cell types.

scholarly journals 616. Tailored Expression of a Transgene to Specific Cell Types in the Central Nervous System After Peripheral Injection of AAV9

2016 ◽  
Vol 24 ◽  
pp. S244
Author(s):  
Eloise Hudry ◽  
Jonathan Dashkoff ◽  
Paul Lerner ◽  
Shuko Takeda ◽  
Nhi Truong ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Types ◽  
Specific Cell ◽  
The Central Nervous System

scholarly journals Dynamic Role of Phospholipases A2 in Health and Diseases in the Central Nervous System

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2963
Author(s):  
Grace Y. Sun ◽  
Xue Geng ◽  
Tao Teng ◽  
Bo Yang ◽  
Michael K. Appenteng ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cellular Localization ◽  
Cell Types ◽  
Molecular Structures ◽  
Specific Cell ◽  
Phospholipases A2 ◽  
Cell Functions ◽  
The Central Nervous System

Phospholipids are major components in the lipid bilayer of cell membranes. These molecules are comprised of two acyl or alkyl groups and different phospho-base groups linked to the glycerol backbone. Over the years, substantial interest has focused on metabolism of phospholipids by phospholipases and the role of their metabolic products in mediating cell functions. The high levels of polyunsaturated fatty acids (PUFA) in the central nervous system (CNS) have led to studies centered on phospholipases A2 (PLA2s), enzymes responsible for cleaving the acyl groups at the sn-2 position of the phospholipids and resulting in production of PUFA and lysophospholipids. Among the many subtypes of PLA2s, studies have centered on three major types of PLA2s, namely, the calcium-dependent cytosolic cPLA2, the calcium-independent iPLA2 and the secretory sPLA2. These PLA2s are different in their molecular structures, cellular localization and, thus, production of lipid mediators with diverse functions. In the past, studies on specific role of PLA2 on cells in the CNS are limited, partly because of the complex cellular make-up of the nervous tissue. However, understanding of the molecular actions of these PLA2s have improved with recent advances in techniques for separation and isolation of specific cell types in the brain tissue as well as development of sensitive molecular tools for analyses of proteins and lipids. A major goal here is to summarize recent studies on the characteristics and dynamic roles of the three major types of PLA2s and their oxidative products towards brain health and neurological disorders.

scholarly journals FIN-Seq: Transcriptional profiling of specific cell types in frozen archived tissue from the human central nervous system

2019 ◽  
Author(s):  
Ryoji Amamoto ◽  
Emanuela Zuccaro ◽  
Nathan C. Curry ◽  
Sonia Khurana ◽  
Hsu-Hsin Chen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Single Cell ◽  
Human Tissue ◽  
Cell Types ◽  
Transcriptional Analysis ◽  
Specific Cell ◽  
Cell Type Specificity ◽  
Human Central Nervous System ◽  
Single Nucleus

ABSTRACTThousands of frozen, archived tissues from postmortem human central nervous system (CNS) are currently available in brain banks. As single cell and single nucleus technologies are beginning to elucidate the cellular diversity present within the human CNS, it is becoming clear that transcriptional analysis of the human CNS requires cell type specificity. Single cell and single nucleus RNA profiling provide one avenue to decipher this heterogeneity. An alternative, complementary approach is to profile isolated, pre-defined cell types and use methods that can be applied to many archived human tissue samples. Here, we developed FIN-Seq (FrozenImmunolabeledNucleiSequencing), a method that accomplishes these goals. FIN-Seq uses immunohisto-chemical isolation of nuclei of specific cell types from frozen human tissue, followed by RNA-Sequencing. We applied this method to frozen postmortem samples of human cerebral cortex and retina and were able to identify transcripts, including low abundance transcripts, in specific cell types.

The zebrafish colourless gene regulates development of non-ectomesenchymal neural crest derivatives

Development ◽  
2000 ◽  
Vol 127 (3) ◽  
pp. 515-525 ◽  
Author(s):  
R.N. Kelsh ◽  
J.S. Eisen
Keyword(s):  
Nervous System ◽  
Neural Crest ◽  
Cell Types ◽  
Pigment Cells ◽  
Specific Cell ◽  
Zebrafish Embryos ◽  
Craniofacial Skeleton ◽  
Cell Fates ◽  
Peripheral Neurons ◽  
Neural Crest Development

Neural crest forms four major categories of derivatives: pigment cells, peripheral neurons, peripheral glia, and ectomesenchymal cells. Some early neural crest cells generate progeny of several fates. How specific cell fates become specified is still poorly understood. Here we show that zebrafish embryos with mutations in the colourless gene have severe defects in most crest-derived cell types, including pigment cells, neurons and specific glia. In contrast, craniofacial skeleton and medial fin mesenchyme are normal. These observations suggest that colourless has a key role in development of non-ectomesenchymal neural crest fates, but not in development of ectomesenchymal fates. Thus, the cls mutant phenotype reveals a segregation of ectomesenchymal and non-ectomesenchymal fates during zebrafish neural crest development. The combination of pigmentation and enteric nervous system defects makes colourless mutations a model for two human neurocristopathies, Waardenburg-Shah syndrome and Hirschsprung's disease.

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