scholarly journals Temperature variability is integrated by a spatially embedded decision-making center to break dormancy in Arabidopsis seeds

2017 ◽  
Vol 114 (25) ◽  
pp. 6629-6634 ◽  
Author(s):  
Alexander T. Topham ◽  
Rachel E. Taylor ◽  
Dawei Yan ◽  
Eiji Nambara ◽  
Iain G. Johnston ◽  
...  
Keyword(s):  
Decision Making ◽  
Variable Temperature ◽  
Spatial Separation ◽  
Cell Types ◽  
Process Variable ◽  
Critical Transitions ◽  
Distinct Cell ◽  
Human Neurons ◽  
Metabolic Interactions ◽  
Time Critical

Plants perceive and integrate information from the environment to time critical transitions in their life cycle. Some mechanisms underlying this quantitative signal processing have been described, whereas others await discovery. Seeds have evolved a mechanism to integrate environmental information by regulating the abundance of the antagonistically acting hormones abscisic acid (ABA) and gibberellin (GA). Here, we show that hormone metabolic interactions and their feedbacks are sufficient to create a bistable developmental fate switch in Arabidopsis seeds. A digital single-cell atlas mapping the distribution of hormone metabolic and response components revealed their enrichment within the embryonic radicle, identifying the presence of a decision-making center within dormant seeds. The responses to both GA and ABA were found to occur within distinct cell types, suggesting cross-talk occurs at the level of hormone transport between these signaling centers. We describe theoretically, and demonstrate experimentally, that this spatial separation within the decision-making center is required to process variable temperature inputs from the environment to promote the breaking of dormancy. In contrast to other noise-filtering systems, including human neurons, the functional role of this spatial embedding is to leverage variability in temperature to transduce a fate-switching signal within this biological system. Fluctuating inputs therefore act as an instructive signal for seeds, enhancing the accuracy with which plants are established in ecosystems, and distributed computation within the radicle underlies this signal integration mechanism.

Fine Structure of the Malpighian Tubules of the Mosquito, Culex pipiens

1971 ◽  
Vol 29 ◽  
pp. 402-403
Author(s):  
Brendan Clifford
Keyword(s):  
Fine Structure ◽  
Culex Pipiens ◽  
Stellate Cell ◽  
Malpighian Tubule ◽  
Cell Types ◽  
Instar Larva ◽  
Malpighian Tubules ◽  
Calliphora Erythrocephala ◽  
Distinct Cell ◽  
Basal Plasma

An ultrastructural investigation of the Malpighian tubules of the fourth instar larva of Culex pipiens was undertaken as part of a continuing study of the fine structure of transport epithelia.Each of the five Malpighian tubules was found to be morphologically identical and regionally undifferentiated. Two distinct cell types, the primary and stellate, were found intermingled along the length of each tubule. The ultrastructure of the stellate cell was previously described in the Malpighian tubule of the blowfly, Calliphora erythrocephala by Berridge and Oschman.The basal plasma membrane of the primary cell is extremely irregular, giving rise to a complex interconnecting network of basal channels. The compartments of cytoplasm entrapped within this system of basal infoldings contain mitochondria, free ribosomes, and small amounts of rough endoplasmic reticulum. The mitochondria are distinctive in that the cristae run parallel to the long axis of the organelle.

scholarly journals Tumour Microenvironment: Roles of the Aryl Hydrocarbon Receptor, O-GlcNAcylation, Acetyl-CoA and Melatonergic Pathway in Regulating Dynamic Metabolic Interactions across Cell Types—Tumour Microenvironment and Metabolism

2020 ◽  
Vol 22 (1) ◽  
pp. 141
Author(s):  
George Anderson
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Glycogen Synthase ◽  
Tumour Progression ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Future Research ◽  
Acetyl Coa ◽  
Dynamic Interactions ◽  
Aryl Hydrocarbon ◽  
Metabolic Interactions

This article reviews the dynamic interactions of the tumour microenvironment, highlighting the roles of acetyl-CoA and melatonergic pathway regulation in determining the interactions between oxidative phosphorylation (OXPHOS) and glycolysis across the array of cells forming the tumour microenvironment. Many of the factors associated with tumour progression and immune resistance, such as yin yang (YY)1 and glycogen synthase kinase (GSK)3β, regulate acetyl-CoA and the melatonergic pathway, thereby having significant impacts on the dynamic interactions of the different types of cells present in the tumour microenvironment. The association of the aryl hydrocarbon receptor (AhR) with immune suppression in the tumour microenvironment may be mediated by the AhR-induced cytochrome P450 (CYP)1b1-driven ‘backward’ conversion of melatonin to its immediate precursor N-acetylserotonin (NAS). NAS within tumours and released from tumour microenvironment cells activates the brain-derived neurotrophic factor (BDNF) receptor, TrkB, thereby increasing the survival and proliferation of cancer stem-like cells. Acetyl-CoA is a crucial co-substrate for initiation of the melatonergic pathway, as well as co-ordinating the interactions of OXPHOS and glycolysis in all cells of the tumour microenvironment. This provides a model of the tumour microenvironment that emphasises the roles of acetyl-CoA and the melatonergic pathway in shaping the dynamic intercellular metabolic interactions of the various cells within the tumour microenvironment. The potentiation of YY1 and GSK3β by O-GlcNAcylation will drive changes in metabolism in tumours and tumour microenvironment cells in association with their regulation of the melatonergic pathway. The emphasis on metabolic interactions across cell types in the tumour microenvironment provides novel future research and treatment directions.

scholarly journals NF-κB in Cancer Immunity: Friend or Foe?

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 355
Author(s):  
Guilhem Lalle ◽  
Julie Twardowski ◽  
Yenkel Grinberg-Bleyer
Keyword(s):  
Immune Responses ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Transcriptional Activators ◽  
New Class ◽  
Complex Interactions ◽  
Cancer Immunity ◽  
Distinct Cell ◽  
Cancer Initiation ◽  
Cancer Outcome

The emergence of immunotherapies has definitely proven the tight relationship between malignant and immune cells, its impact on cancer outcome and its therapeutic potential. In this context, it is undoubtedly critical to decipher the transcriptional regulation of these complex interactions. Following early observations demonstrating the roles of NF-κB in cancer initiation and progression, a series of studies converge to establish NF-κB as a master regulator of immune responses to cancer. Importantly, NF-κB is a family of transcriptional activators and repressors that can act at different stages of cancer immunity. In this review, we provide an overview of the selective cell-intrinsic contributions of NF-κB to the distinct cell types that compose the tumor immune environment. We also propose a new view of NF-κB targeting drugs as a new class of immunotherapies for cancer.

scholarly journals Glucocorticoid Receptor β (GRβ): Beyond Its Dominant-Negative Function

2021 ◽  
Vol 22 (7) ◽  
pp. 3649
Author(s):  
Patricia Ramos-Ramírez ◽  
Omar Tliba
Keyword(s):  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Cell Communication ◽  
Cell Types ◽  
The Body ◽  
Dominant Negative ◽  
Negative Effects ◽  
Independent Manner ◽  
Distinct Cell ◽  
Induced Apoptosis

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GRα and GRβ, generated through alternative splicing mechanisms. While GRα is the classic receptor responsible for GC actions, GRβ has been implicated in the impairment of GRα-mediated activities. Interestingly, in contrast to the popular belief that GRβ actions are restricted to its dominant-negative effects on GRα-mediated responses, GRβ has been shown to have intrinsic activities and “directly” regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GRα-independent manner. Furthermore, GRβ has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GRβ-mediated responses, with a focus on the GRα-independent/intrinsic effects of GRβ and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.

scholarly journals Development, characterization, and applications of multi-material stereolithography bioprinting

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bagrat Grigoryan ◽  
Daniel W. Sazer ◽  
Amanda Avila ◽  
Jacob L. Albritton ◽  
Aparna Padhye ◽  
...  
Keyword(s):  
Material Selection ◽  
Cell Types ◽  
Fluorescent Tracers ◽  
Regional Feature ◽  
Multicellular Aggregates ◽  
Distinct Cell ◽  
Adenocarcinoma Cells ◽  
Mammalian Tissues ◽  
Heterotypic Interactions ◽  
Feature Alignment

AbstractAs a 3D bioprinting technique, hydrogel stereolithography has historically been limited in its ability to capture the spatial heterogeneity that permeates mammalian tissues and dictates structure–function relationships. This limitation stems directly from the difficulty of preventing unwanted material mixing when switching between different liquid bioinks. Accordingly, we present the development, characterization, and application of a multi-material stereolithography bioprinter that provides controlled material selection, yields precise regional feature alignment, and minimizes bioink mixing. Fluorescent tracers were first used to highlight the broad design freedoms afforded by this fabrication strategy, complemented by morphometric image analysis to validate architectural fidelity. To evaluate the bioactivity of printed gels, 344SQ lung adenocarcinoma cells were printed in a 3D core/shell architecture. These cells exhibited native phenotypic behavior as evidenced by apparent proliferation and formation of spherical multicellular aggregates. Cells were also printed as pre-formed multicellular aggregates, which appropriately developed invasive protrusions in response to hTGF-β1. Finally, we constructed a simplified model of intratumoral heterogeneity with two separate sub-populations of 344SQ cells, which together grew over 14 days to form a dense regional interface. Together, these studies highlight the potential of multi-material stereolithography to probe heterotypic interactions between distinct cell types in tissue-specific microenvironments.

scholarly journals Annotation of chromatin states in 66 complete mouse epigenomes during development

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Arjan van der Velde ◽  
Kaili Fan ◽  
Junko Tsuji ◽  
Jill E. Moore ◽  
Michael J. Purcaro ◽  
...  
Keyword(s):  
Target Genes ◽  
Cell Types ◽  
Developmental Trajectory ◽  
Phase Iii ◽  
Chromatin State ◽  
Mammalian Development ◽  
Chromatin States ◽  
Transcription Start Sites ◽  
Repressive Mark ◽  
Distinct Cell

AbstractThe morphologically and functionally distinct cell types of a multicellular organism are maintained by their unique epigenomes and gene expression programs. Phase III of the ENCODE Project profiled 66 mouse epigenomes across twelve tissues at daily intervals from embryonic day 11.5 to birth. Applying the ChromHMM algorithm to these epigenomes, we annotated eighteen chromatin states with characteristics of promoters, enhancers, transcribed regions, repressed regions, and quiescent regions. Our integrative analyses delineate the tissue specificity and developmental trajectory of the loci in these chromatin states. Approximately 0.3% of each epigenome is assigned to a bivalent chromatin state, which harbors both active marks and the repressive mark H3K27me3. Highly evolutionarily conserved, these loci are enriched in silencers bound by polycomb repressive complex proteins, and the transcription start sites of their silenced target genes. This collection of chromatin state assignments provides a useful resource for studying mammalian development.

microRNA-252 and FoxO repress inflammaging by a dual inhibitory mechanism on Dawdle mediated TGF-β pathway in Drosophila

Genetics ◽  
2021 ◽  
Author(s):  
Xiaofen Wu ◽  
Kongyan Niu ◽  
Xiaofan Wang ◽  
Jing Zhao ◽  
Han Wang ◽  
...  
Keyword(s):  
Cell Types ◽  
Innate Immune ◽  
Low Grade ◽  
Sequencing Analysis ◽  
Immune Genes ◽  
Healthy Longevity ◽  
Muscle Tissues ◽  
Distinct Cell ◽  
A Cell ◽  
Innate Immune Genes

Abstract Inflammaging refers to low-grade, chronically activated innate immunity that has deleterious effects on healthy lifespan. However, little is known about the intrinsic signaling pathway that elicits innate immune genes during aging. Here using Drosophila melanogaster, we profile the microRNA targetomes in young and aged animals, and reveal Dawdle (Daw), an activin-like ligand of the TGF-β pathway, as a physiological target of microRNA-252 (miR-252). We show that miR-252 cooperates with Forkhead box O (FoxO), a conserved transcriptional factor implicated in aging, to repress Daw. Unopposed Daw triggers hyper activation of innate immune genes coupled with a decline in organismal survival. Using adult muscle tissues, single-cell sequencing analysis describes that Daw and its downstream innate immune genes are expressed in distinct cell types, suggesting a cell non-autonomous mode of regulation. We further determine the genetic cascade by which Daw signaling leads to increased Kenny/IKKγ protein, which in turn activates Relish/NF-κB protein and consequentially innate immune genes. Finally, transgenic increase of miR-252 and FoxO pathway factors in wild-type Drosophila extends lifespan and mitigates the induction of innate immune genes in aging. Together, we propose that miR-252 and FoxO promote healthy longevity by cooperative inhibition on Daw mediated inflammaging.

Abstract 415: Cardioprotective Effects of Interleukin-15 in Immortalized Human Ventricular Cardiomyocytes

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Marin Jane McBride ◽  
Kristina Durham ◽  
Bernardo L Trigatti
Keyword(s):  
Stress Response ◽  
Er Stress ◽  
Interleukin 2 ◽  
Cell Types ◽  
Human Cardiomyocytes ◽  
Er Stress Response ◽  
Distinct Cell ◽  
Receptor Chain ◽  
Interleukin 15 ◽  
Receptor Beta

Interleukin-15 (IL-15) is a pleotropic cytokine that has a profound effect on the proliferation, survival and differentiation of many distinct cell types. The IL-15 receptor complex has 3 subunits: the unique receptor chain IL-15 receptor alpha (IL-15Rα), and two receptor chains shared with interleukin-2 (IL-2) and/or other cytokines, referred to as IL-2 receptor beta (IL-2Rβ) and IL-2 receptor gamma/gamma common chain (IL-2Rγ/γc), respectively. To our knowledge, this is the first study to examine the effects of IL-15 in immortalized human cardiomyocytes. Data collected by RT-PCR shows mRNA expression of IL-15Rα, IL-2Rβ and IL-2 Rγ/γc in these cells. Additionally, western blotting for IL-15Rα, IL-2Rβ and IL-2 Rγ/γc confirms the presence of all three IL-15 receptors. Early experiments examining the effect of IL-15 on cardiomyocyte cell survival show a statistically significant protective effect of IL-15 on the survival of cells exposed to tunicamycin, a pharamacological endoplasmic reticulum (ER) stress inducing agent. These findings suggest that IL-15 signaling may be an important cardioprotective pathway that is involved in the cardiac ER stress response. As ER stress is a major component of multiple different cardiac pathologies, such as myocardial infarction, heart failure and diabetes, uncovering the molecular mechanism by which IL-15 protects the heart will allow for deeper understanding of the cardiac ER stress response.

scholarly journals Simultaneous profiling of multiple chromatin proteins in the same cells

2021 ◽  
Author(s):  
Sneha Gopalan ◽  
Yuqing Wang ◽  
Nicholas W. Harper ◽  
Manuel Garber ◽  
Thomas G Fazzio
Keyword(s):  
Rna Polymerase Ii ◽  
Direct Analysis ◽  
Cell Types ◽  
Regulatory Elements ◽  
Genome Wide ◽  
Distinct Cell ◽  
Direct Measurements ◽  
Cell Type Specific ◽  
Chromatin Proteins

Methods derived from CUT&RUN and CUT&Tag enable genome-wide mapping of the localization of proteins on chromatin from as few as one cell. These and other mapping approaches focus on one protein at a time, preventing direct measurements of co-localization of different chromatin proteins in the same cells and requiring prioritization of targets where samples are limiting. Here we describe multi-CUT&Tag, an adaptation of CUT&Tag that overcomes these hurdles by using antibody-specific barcodes to simultaneously map multiple proteins in the same cells. Highly specific multi-CUT&Tag maps of histone marks and RNA Polymerase II uncovered sites of co-localization in the same cells, active and repressed genes, and candidate cis-regulatory elements. Single-cell multi-CUT&Tag profiling facilitated identification of distinct cell types from a mixed population and characterization of cell type-specific chromatin architecture. In sum, multi-CUT&Tag increases the information content per cell of epigenomic maps, facilitating direct analysis of the interplay of different proteins on chromatin.

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