scholarly journals MAGE cancer-testis antigens protect the mammalian germline under environmental stress

2019 ◽  
Vol 5 (5) ◽  
pp. eaav4832 ◽  
Author(s):  
Klementina Fon Tacer ◽  
Marhiah C. Montoya ◽  
Melissa J. Oatley ◽  
Tessa Lord ◽  
Jon M. Oatley ◽  
...  
Keyword(s):  
Environmental Stress ◽  
Genotoxic Stress ◽  
Stem Cell Maintenance ◽  
Fuel Switching ◽  
Male Germline ◽  
Species Survival ◽  
The Face ◽  
Melanoma Antigens ◽  
Reproductive Rates

Ensuring robust gamete production even in the face of environmental stress is of utmost importance for species survival, especially in mammals that have low reproductive rates. Here, we describe a family of genes called melanoma antigens (MAGEs) that evolved in eutherian mammals and are normally restricted to expression in the testis (http://MAGE.stjude.org) but are often aberrantly activated in cancer. Depletion of Mage-a genes disrupts spermatogonial stem cell maintenance and impairs repopulation efficiency in vivo. Exposure of Mage-a knockout mice to genotoxic stress or long-term starvation that mimics famine in nature causes defects in spermatogenesis, decreased testis weights, diminished sperm production, and reduced fertility. Last, human MAGE-As are activated in many cancers where they promote fuel switching and growth of cells. These results suggest that mammalian-specific MAGE genes have evolved to protect the male germline against environmental stress, ensure reproductive success under non-optimal conditions, and are hijacked by cancer cells.

Molecular basis of adaptive evolution of sperm motility involved in in vivo fertilization of terrestrial animals

Impact ◽  
2020 ◽  
Vol 2020 (6) ◽  
pp. 73-75
Author(s):  
Akihiko Watanabe
Keyword(s):  
Sexual Reproduction ◽  
Sperm Motility ◽  
Asexual Reproduction ◽  
Acrosome Reaction ◽  
Sperm Morphology ◽  
Adaptive Potential ◽  
Selective Pressures ◽  
The Face ◽  
Genetic Profiles

One of the unifying traits of life on this planet is reproduction, or life's ability to make copies of itself. The mode of reproduction has evolved over time, having almost certainly begun with simple asexual reproduction when the ancestral single celled organism divided into two. Since these beginnings' life has tried out numerous strategies, and perhaps one of the most important and successful has been sexual reproduction. This form of reproduction relies on the union of gametes, otherwise known as sperm and egg. Evolutionarily, sexual reproduction allows for greater adaptive potential because the genes of two unique individuals have a chance to recombine and mix in order to produce a new individual. Unlike asexual reproduction which produces genetically-identical clones of the parent individual, sex produces offspring with novel genes and combinations of genes. Therefore, in the face of new selective pressures there is a higher chance that one of these novel genetic profiles will produce an adaptation that is advantageous in the new circumstances. Dr Akihiko Watanabe is a reproductive biologist based in the Department of Biology, Faculty of Science Yamagata University in Japan, he is currently working on three research projects; a comparative study on the signalling pathways for inducing sperm motility and acrosome reaction in amphibians, the mechanism behind the adaptive modification of sperm morphology and motility, and the origin of sperm motility initiating substance (SMIS).

scholarly journals Set1 Targets Genes with Essential Identity and Tumor-Suppressing Functions in Planarian Stem Cells

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1182
Author(s):  
Prince Verma ◽  
Court K. M. Waterbury ◽  
Elizabeth M. Duncan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mammalian Cells ◽  
Cell Function ◽  
Genotoxic Stress ◽  
Specific Gene ◽  
Cell Identity ◽  
Chromatin Signature ◽  
Lysine Methyltransferase

Tumor suppressor genes (TSGs) are essential for normal cellular function in multicellular organisms, but many TSGs and tumor-suppressing mechanisms remain unknown. Planarian flatworms exhibit particularly robust tumor suppression, yet the specific mechanisms underlying this trait remain unclear. Here, we analyze histone H3 lysine 4 trimethylation (H3K4me3) signal across the planarian genome to determine if the broad H3K4me3 chromatin signature that marks essential cell identity genes and TSGs in mammalian cells is conserved in this valuable model of in vivo stem cell function. We find that this signature is indeed conserved on the planarian genome and that the lysine methyltransferase Set1 is largely responsible for creating it at both cell identity and putative TSG loci. In addition, we show that depletion of set1 in planarians induces stem cell phenotypes that suggest loss of TSG function, including hyperproliferation and an abnormal DNA damage response (DDR). Importantly, this work establishes that Set1 targets specific gene loci in planarian stem cells and marks them with a conserved chromatin signature. Moreover, our data strongly suggest that Set1 activity at these genes has important functional consequences both during normal homeostasis and in response to genotoxic stress.

scholarly journals Antibacterial and In Vivo Studies of a Green, One-Pot Preparation of Copper/Zinc Oxide Nanoparticle-Coated Bandages

Membranes ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 462
Author(s):  
Archana R. Deokar ◽  
Ilana Perelshtein ◽  
Melissa Saibene ◽  
Nina Perkas ◽  
Paride Mantecca ◽  
...  
Keyword(s):  
Zinc Oxide ◽  
Metal Oxide ◽  
Ultrasound Irradiation ◽  
Face Mask ◽  
In Vivo Studies ◽  
One Pot ◽  
The Face ◽  
Bulk Scale ◽  
Particle Size And Shape

Simultaneous water and ethanol-based synthesis and coating of copper and zinc oxide (CuO/ZnO) nanoparticles (NPs) on bandages was carried out by ultrasound irradiation. High resolution-transmission electron microscopy demonstrated the effects of the solvent on the particle size and shape of metal oxide NPs. An antibacterial activity study of metal-oxide-coated bandages was carried out against Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative). CuO NP-coated bandages made from both water and ethanol demonstrated complete killing of S. aureus and E. coli bacteria within 30 min., whereas ZnO NP-coated bandages demonstrated five-log reductions in viability for both kinds of bacteria after 60 min of interaction. Further, the antibacterial mechanism of CuO/ZnO NP-coated bandages is proposed here based on electron spin resonance studies. Nanotoxicology investigations were conducted via in vivo examinations of the effect of the metal-oxide bandages on frog embryos (teratogenesis assay—Xenopus). The results show that water-based coatings resulted in lesser impacts on embryo development than the ethanol-based ones. These bandages should therefore be considered safer than the ethanol-based ones. The comparison between the toxicity of the metal oxide NPs prepared in water and ethanol is of great importance, because water will replace ethanol for bulk scale synthesis of metal oxide NPs in commercial companies to avoid further ignition problems. The novelty and importance of this manuscript is avoiding the ethanol in the typical water:ethanol mixture as the solvent for the preparation of metal oxide NPs. Ethanol is ignitable, and commercial companies are trying the evade its use. This is especially important these days, as the face mask produced by sonochemistry (SONOMASK) is being sold all over the world by SONOVIA, and it is coated with ZnO.

CD200 is a novel p53-target gene involved in apoptosis-associated immune tolerance

Blood ◽  
2004 ◽  
Vol 103 (7) ◽  
pp. 2691-2698 ◽  
Author(s):  
Michael D. Rosenblum ◽  
Edit Olasz ◽  
Jeffery E. Woodliff ◽  
Bryon D. Johnson ◽  
Marja C. Konkol ◽  
...  
Keyword(s):  
Target Gene ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Immune Reactivity ◽  
Biochemical Processes ◽  
The Face ◽  
P53 Target Gene ◽  
Self Antigens

Abstract During apoptotic cell death, biochemical processes modify self-proteins and create potential autoantigens. To maintain self-tolerance in the face of natural cell turnover, the immune system must prevent or control responses to apoptosis-associated autoantigens or risk autoimmunity. The molecular mechanisms governing this process remain largely unknown. Here, we show that expression of the immunoregulatory protein CD200 increases as murine dendritic cells (DCs) undergo apoptosis. We define CD200 as a p53-target gene and identify both p53- and caspase-dependent pathways that control CD200 expression during apoptosis. CD200 expression on apoptotic DCs diminishes proinflammatory cytokine production in response to self-antigens in vitro and is required for UVB-mediated tolerance to haptenated self-proteins in vivo. Up-regulation of CD200 may represent a novel mechanism, whereby immune reactivity to apoptosis-associated self-antigens is suppressed under steady state conditions. (Blood. 2004;103: 2691-2698)

scholarly journals SENSITIVITY TO ENVIRONMENTAL STRESS OF PRATA,JAPIRA AND VITÓRIA BANANA CULTIVARS PROVEN BY CHLOROPHYLL a FLUORESCENCE

2017 ◽  
Vol 39 (2) ◽  
Author(s):  
PRISCILA NOBRES DOS SANTOS ◽  
DIOLINA MOURA SILVA ◽  
CAMILLA ZANOTTI GALLON ◽  
JOSÉ AIRES VENTURA
Keyword(s):  
Environmental Stress ◽  
Chlorophyll A ◽  
Chlorophyll A Fluorescence ◽  
Physiological Responses ◽  
Fluorescence Emission ◽  
Conservation Of Energy ◽  
Post Harvest ◽  
Mda Content ◽  
Two Stages

ABSTRACT This study aimed to evaluate the physiological responses to environmental stress during pre- and post-harvest of the following banana cultivars: Prata (AAB), Japira (AAAB) and Vitoria (AAAB). Analyses were carried out on young plants at vegetative stage (daughter-plant) and adult plants at reproductive stage (motherplant). The experimental design was completely randomized. In the in vivo pre-harvest analysis were used seven replications, in a factorial scheme (3x2x2), three cultivars and two stages (vegetative and reproductive) and two collection periods (March and June). For the analysis of post-harvest quality were used five replications in a factorial design (3x2x5), corresponding to three cultivars, two development stages and five periods of post-harvest analysis, carried out every two days from stage 4 of fruit ripening. The chlorophyll a fluorescence emission kinetics showed low photochemical performance of the three cultivars in June, a period characterized by lower temperatures and water deficit. Prata was the cultivar with the lowest tolerance to abiotic physiological behavior changes, which also reflected in fruit quality, because there was a change in physical and physicochemical parameters. Japira and Vitoria cultivars showed similar physiological responses in the pre- and post-harvest periods, according to their phylogenetic proximity. The total performance index, i.e., the conservation of energy absorbed by PSII up to the reduction of the final PSI acceptors (PItotal) and the di-malonic aldehyde (MDA) content were significantly higher in Japira and Vitoria cultivars compared to Prata cultivar in the reproductive phase. There was no significant change in the potential quantum efficiency of PSII (FV / FM = jP0) among the three cultivars. It was concluded that Japira and Vitoria cultivars showed greater plasticity to tolerate or even adapt to abiotic variations keeping higher fruit yield. PItotal is the most sensitive parameter during the banana life cycle and important tool for distinguishing different cultivars yields.

scholarly journals Notch-dependent DNA cis-regulatory elements and their dose-dependent control of C. elegans stem cell self-renewal

2021 ◽  
Author(s):  
Tina R. Lynch ◽  
Mingyu Xue ◽  
Cazza W. Czerniak ◽  
ChangHwan Lee ◽  
Judith Kimble
Keyword(s):  
Stem Cell ◽  
Regulatory Elements ◽  
Single Element ◽  
Developmental Context ◽  
C Elegans ◽  
Stem Cell Maintenance ◽  
Nascent Transcripts ◽  
Functional Analyses ◽  
Dose Dependent

A long-standing biological question is how DNA cis-regulatory elements shape transcriptional patterns during metazoan development. The use of reporter constructs, cell culture and computational modeling has made enormous contributions to understanding this fundamental question, but analysis of regulatory elements in their natural developmental context is an essential but rarely used complement. Here, we edited Notch-dependent cis-regulatory elements in the endogenous C. elegans sygl-1 gene, which encodes a key stem cell regulator. We then analyzed the in vivo consequences of those mutations – on both gene expression (nascent transcripts, mRNA, protein) and stem cell maintenance. Mutation of a single element in a three-element homotypic cluster reduced expression as well as stem cell pool size by about half, while mutation of two elements essentially abolished them. We find that LBS number and LBS neighborhood are both important to activity: elements on separate chromosomes function additively, while elements in the same cluster act synergistically. Our approach of precise CRISPR/Cas9 gene editing coupled with quantitation of both molecular and biological readouts establishes a powerful model for in vivo functional analyses of DNA cis-regulatory elements.

scholarly journals me31B regulates stem cell homeostasis by preventing excess dedifferentiation in the Drosophila male germline

2021 ◽  
Author(s):  
Lindy Jensen ◽  
Zsolt G. Venkei ◽  
George J. Watase ◽  
Bitarka Bisai ◽  
Scott Pletcher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Critical Role ◽  
Stem Cell Population ◽  
Germline Stem Cells ◽  
Cell Identity ◽  
Stem Cell Maintenance ◽  
Differentiated Cells ◽  
Male Germline ◽  
Elevated Frequency

Tissue-specific stem cells maintain tissue homeostasis by providing a continuous supply of differentiated cells throughout the life of organisms. Differentiated/differentiating cells can revert back to a stem cell identity via dedifferentiation to help maintain the stem cell pool beyond the lifetime of individual stem cells. Although dedifferentiation is important to maintain the stem cell population, it is speculated to underlie tumorigenesis. Therefore, this process must be tightly controlled. Here we show that a translational regulator me31B plays a critical role in preventing excess dedifferentiation in the Drosophila male germline: in the absence of me31B, spermatogonia (SGs) dedifferentiate into germline stem cells (GSCs) at a dramatically elevated frequency. Our results show that the excess dedifferentiation is likely due to misregulation of nos, a key regulator of germ cell identity and GSC maintenance. Taken together, our data reveal negative regulation of dedifferentiation to balance stem cell maintenance with differentiation.

scholarly journals Mechanics of the cellular microenvironment as perceived by cells in vivo

2021 ◽  
Author(s):  
Alessandro Mongera ◽  
Marie Pochitaloff ◽  
Hannah J. Gustafson ◽  
Georgina A. Stooke-Vaughan ◽  
Payam Rowghanian ◽  
...  
Keyword(s):  
Stress Relaxation ◽  
Mechanical Parameters ◽  
Cellular Microenvironment ◽  
Stem Cell Maintenance ◽  
Quantitative Studies ◽  
Cell Proliferation And Differentiation ◽  
3D Microenvironment ◽  
Proliferation And Differentiation

Tissue morphogenesis and repair, as well as organ homeostasis, require cells to constantly monitor their 3D microenvironment and adapt their behaviors in response to local biochemical and mechanical cues1-6. In vitro studies have shown that substrate stiffness and stress relaxation are important mechanical parameters in the control of cell proliferation and differentiation, stem cell maintenance, cell migration 7-11, as well as tumor progression and metastasis12,13. Yet, the mechanical parameters of the microenvironment that cells perceive in vivo, within 3D tissues, remain unknown. In complex materials with strain- and time-dependent material properties, the perceived mechanical parameters depend both on the strain and timescales at which the material is mechanically probed14. Here, we quantify in vivo and in situ the mechanics of the cellular microenvironment that cells probe during vertebrate presomitic mesoderm (PSM) specification. By analyzing the magnitude and dynamics of endogenous, cell-generated strains, we show that individual cells preferentially probe the stiffness associated with deformations of the supracellular, foam-like tissue architecture. We reveal how stress relaxation leads to a perceived microenvironment stiffness that decreases over time, with cells probing the softest regime. While stress relaxation timescales are spatially uniform in the tissue, most mechanical parameters, including those probed by cells, vary along the anteroposterior axis, as mesodermal progenitors commit to different lineages. Understanding the mechanical parameters that cells probe in their native 3D environment is important for quantitative studies of mechanosensation in vivo2-4,6,15 and can help design scaffolds for tissue engineering applications16-18.

scholarly journals A novel Axin2 knock-in mouse model for visualization and lineage tracing of WNT/CTNNB1 responsive cells

2020 ◽  
Author(s):  
Anoeska Agatha Alida van de Moosdijk ◽  
Yorick Bernardus Cornelis van de Grift ◽  
Saskia Madelon Ada de Man ◽  
Amber Lisanne Zeeman ◽  
Renée van Amerongen
Keyword(s):  
Cell Fate ◽  
Mouse Strain ◽  
Critical Role ◽  
Lineage Tracing ◽  
Fluorescent Reporter ◽  
Cell Fate Decisions ◽  
Stem Cell Maintenance ◽  
Signaling Dynamics ◽  
Before And After

AbstractWnt signal transduction controls tissue morphogenesis, maintenance and regeneration in all multicellular animals. In mammals, the WNT/CTNNB1 (Wnt/β-catenin) pathway controls cell proliferation and cell fate decisions before and after birth. It plays a critical role at multiple stages of embryonic development, but also governs stem cell maintenance and homeostasis in adult tissues. However, it remains challenging to monitor endogenous WNT/CTNNB1 signaling dynamics in vivo. Here we report the generation and characterization of a new knock-in mouse strain that doubles as a fluorescent reporter and lineage tracing driver for WNT/CTNNB1 responsive cells. We introduced a multi-cistronic targeting cassette at the 3’ end of the universal WNT/CTNNB1 target gene Axin2. The resulting knock-in allele expresses a bright fluorescent reporter (3xNLS-SGFP2) and a doxycycline-inducible driver for lineage tracing (rtTA3). We show that the Axin2P2A-rtTA3-T2A-3xNLS-SGFP2 strain labels WNT/CTNNB1 cells at multiple anatomical sites during different stages of embryonic and postnatal development. It faithfully reports the subtle and dynamic changes in physiological WNT/CTNNB1 signaling activity that occur in vivo. We expect this mouse strain to be a useful resource for biologists who want to track and trace the location and developmental fate of WNT/CTNNB1 responsive stem cells in different contexts.Abstract Figure

scholarly journals Enteroendocrine and tuft cells support Lgr5 stem cells on Paneth cell depletion

2019 ◽  
Vol 116 (52) ◽  
pp. 26599-26605 ◽  
Author(s):  
Johan H. van Es ◽  
Kay Wiebrands ◽  
Carmen López-Iglesias ◽  
Marc van de Wetering ◽  
Laura Zeinstra ◽  
...  
Keyword(s):  
Stem Cells ◽  
Receptor Gene ◽  
Paneth Cell ◽  
Paneth Cells ◽  
Alternative Source ◽  
Stem Cell Maintenance ◽  
Diphtheria Toxin Receptor ◽  
Tuft Cells ◽  
Toxin Receptor

Cycling intestinal Lgr5+stem cells are intermingled with their terminally differentiated Paneth cell daughters at crypt bottoms. Paneth cells provide multiple secreted (e.g., Wnt, EGF) as well as surface-bound (Notch ligand) niche signals. Here we show that ablation of Paneth cells in mice, using a diphtheria toxin receptor gene inserted into the P-lysozyme locus, does not affect the maintenance of Lgr5+stem cells. Flow cytometry, single-cell sequencing, and histological analysis showed that the ablated Paneth cells are replaced by enteroendocrine and tuft cells. As these cells physically occupy Paneth cell positions between Lgr5 stem cells, they serve as an alternative source of Notch signals, which are essential for Lgr5+stem cell maintenance. Our combined in vivo results underscore the adaptive flexibility of the intestine in maintaining normal tissue homeostasis.

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