Cell Competition, the Kinetics of Thymopoiesis, and Thymus Cellularity Are Regulated by Double-Negative 2 to 3 Early Thymocytes

SUMMARYCell competition in the thymus is a homeostatic process that drives turnover. If the process is impaired, thymopoiesis can be autonomously maintained for several weeks, but this causes leukemia. We aimed to understand the impact of cell competition on thymopoiesis, identify the cells involved and determine how the process is regulated. Using thymus transplantation experiments we found that cell competition occurs within the double negative 2 (DN2) and 3 early (DN3e) thymocytes and inhibits thymus autonomy. Furthermore, the expansion of DN2b is regulated by a negative feedback loop imposed by double positive thymocytes and determines the kinetics of thymopoiesis. This feedback loop impacts on cell cycle duration of DN2b, in a response controlled by interleukin 7 availability. Altogether, we show that thymocytes do not merely follow a pre-determined path if provided with the correct signals. Instead, thymopoiesis dynamically integrates cell autonomous and non-cell autonomous aspects that fine-tune normal thymus function.

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A Patient with Double-Negative VGKC, Peripheral Nerve Hyperexcitability, and Central Nervous System Symptoms: A Postinfectious Autoimmune Disease

Case Reports in Neurological Medicine ◽

10.1155/2020/3579419 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Birte Eikeland

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Autoimmune Disease ◽

Peripheral Nerve ◽

Skin Lesions ◽

Double Negative ◽

Pathogenic Potential ◽

Peripheral Nerve Hyperexcitability ◽

Systemic Symptoms ◽

Kinetics Of

Research in the last few years has indicated that most voltage-gated potassium channel- (VGKC-) complex antibodies without leucine-rich glioma-inactivated protein 1 or contactin-associated protein-like 2 antibody specificity lack pathogenic potential and are not clear markers for autoimmune inflammation. Here we report on a patient with double-negative VGKC who developed severe peripheral nerve hyperexcitability, central nervous system symptoms with agitation and insomnia, dysautonomia, and systemic symptoms with weight loss, itch, and skin lesions. The disease started acutely one month after an episode of enteroviral pericarditis and responded well to immunotherapy. The patient is presumed to have developed a postinfectious immunotherapy-responsive autoimmune disease. In the setting of anti-VGKC positivity, it seems likely that anti-VGKC contributed to the pathogenesis of the patient’s symptoms of nerve hyperexcitability and that the disease was caused by an acquired autoimmune effect on the neuronal kinetics of VGKC. It is still unknown whether or not there are unidentified extracellular molecular targets within the VGKC-complex, i.e., a novel surface antigen and a pathogenic antibody that can cause affected individuals to develop a peripheral nerve hyperexcitability syndrome. This case highlights the fact that less well-characterized autoimmune central and peripheral nervous system syndromes may have infectious triggers.

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Self-renewal of double negative 3 (DN3) early thymocytes allows for thymus autonomy but compromises the β-selection checkpoint

10.1101/2020.06.09.142596 ◽

2020 ◽

Author(s):

Rafael A. Paiva ◽

António G. G. Sousa ◽

Camila V. Ramos ◽

Mariana Ávila ◽

Jingtao Lilue ◽

...

Keyword(s):

T Lymphocyte ◽

Target Gene ◽

Gene Signature ◽

Double Negative ◽

Transcriptional Program ◽

Cell Competition ◽

Self Renewal ◽

Atypical Cells ◽

Cellular Turnover

ABSTRACTT lymphocyte differentiation in the thymus relies on high cellular turnover, and cell competition enforces thymocyte replenishment. If deprived of competent progenitors, the thymus can maintain thymopoiesis autonomously for several weeks but this bears a high risk of leukemia. Here we show that double negative 3 early (DN3e) thymocytes can acquire stem cell like properties, which enables them to maintain thymopoiesis. Specifically, DN3e proved to be long-lived, they proliferated and differentiated in vivo, were necessary for autonomous thymopoiesis, and included DNA-label-retaining cells. Single cell RNAseq revealed a transcriptional program of thymopoiesis similar in autonomy and the controls. Nevertheless, a new population was identified in thymus autonomy that was enriched for an aberrant Notch target gene signature and bypassed the β−selection checkpoint. In sum, DN3e have the potential to self-renew and differentiate in vivo if cell competition is compromised but this enables the accumulation of atypical cells, probably leading to leukemia.

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Cell-scale biophysical determinants of cell competition in epithelia

eLife ◽

10.7554/elife.61011 ◽

2021 ◽

Vol 10 ◽

Author(s):

Daniel Gradeci ◽

Anna Bove ◽

Giulia Vallardi ◽

Alan R Lowe ◽

Shiladitya Banerjee ◽

...

Keyword(s):

Conceptual Understanding ◽

High Time Resolution ◽

Cell Level ◽

Cell Competition ◽

Agent Based ◽

Multi Scale ◽

Cellular Factors ◽

The Difference ◽

Outstanding Question ◽

Kinetics Of

How cells with different genetic makeups compete in tissues is an outstanding question in developmental biology and cancer research. Studies in recent years have revealed that cell competition can either be driven by short-range biochemical signalling or by long-range mechanical stresses in the tissue. To date, cell competition has generally been characterised at the population scale, leaving the single-cell-level mechanisms of competition elusive. Here, we use high time-resolution experimental data to construct a multi-scale agent-based model for epithelial cell competition and use it to gain a conceptual understanding of the cellular factors that governs competition in cell populations within tissues. We find that a key determinant of mechanical competition is the difference in homeostatic density between winners and losers, while differences in growth rates and tissue organisation do not affect competition end result. In contrast, the outcome and kinetics of biochemical competition is strongly influenced by local tissue organisation. Indeed, when loser cells are homogenously mixed with winners at the onset of competition, they are eradicated; however, when they are spatially separated, winner and loser cells coexist for long times. These findings suggest distinct biophysical origins for mechanical and biochemical modes of cell competition.

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Direct observations of radiation-enhanced transformations in glass

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100075543 ◽

1983 ◽

Vol 41 ◽

pp. 354-355

Author(s):

J. F. DeNatale ◽

D. G. Howitt

Keyword(s):

Glass Matrix ◽

Diffusion Mechanism ◽

Bubble Formation ◽

Silicate Glasses ◽

Phase Decomposition ◽

Direct Observations ◽

Thin Foils ◽

Oxygen Bubble ◽

Electron Energy Loss ◽

Kinetics Of

The electron irradiation of silicate glasses containing metal cations produces various types of phase separation and decomposition which includes oxygen bubble formation at intermediate temperatures figure I. The kinetics of bubble formation are too rapid to be accounted for by oxygen diffusion but the behavior is consistent with a cation diffusion mechanism if the amount of oxygen in the bubble is not significantly different from that in the same volume of silicate glass. The formation of oxygen bubbles is often accompanied by precipitation of crystalline phases and/or amorphous phase decomposition in the regions between the bubbles and the detection of differences in oxygen concentration between the bubble and matrix by electron energy loss spectroscopy cannot be discerned (figure 2) even when the bubble occupies the majority of the foil depth.The oxygen bubbles are stable, even in the thin foils, months after irradiation and if van der Waals behavior of the interior gas is assumed an oxygen pressure of about 4000 atmospheres must be sustained for a 100 bubble if the surface tension with the glass matrix is to balance against it at intermediate temperatures.

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Irradiation behavior of pyrolytic silicon carbide

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100074288 ◽

1983 ◽

Vol 41 ◽

pp. 72-73

Author(s):

R. J. Lauf

Keyword(s):

Silicon Carbide ◽

Fission Products ◽

Thermodynamics And Kinetics ◽

Neutron Fluences ◽

Fuel Particles ◽

Sic Coatings ◽

Irradiation Behavior ◽

Kinetics Of ◽

Htgr Fuel

Fuel particles for the High-Temperature Gas-Cooled Reactor (HTGR) contain a layer of pyrolytic silicon carbide to act as a miniature pressure vessel and primary fission product barrier. Optimization of the SiC with respect to fuel performance involves four areas of study: (a) characterization of as-deposited SiC coatings; (b) thermodynamics and kinetics of chemical reactions between SiC and fission products; (c) irradiation behavior of SiC in the absence of fission products; and (d) combined effects of irradiation and fission products. This paper reports the behavior of SiC deposited on inert microspheres and irradiated to fast neutron fluences typical of HTGR fuel at end-of-life.

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The Ordered Phase Formation in Ti-Al-Ga Alloys

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100069193 ◽

1970 ◽

Vol 28 ◽

pp. 440-441

Author(s):

Shiro Fujishiro ◽

Harold L. Gegel

Keyword(s):

Thermal Stability ◽

High Temperature ◽

Titanium Alloys ◽

Growth Kinetics ◽

Stoichiometric Composition ◽

Good Potential ◽

Alpha Titanium ◽

Cold Rolled ◽

Kinetics Of ◽

Thermal Stability Of

Ordered-alpha titanium alloys having a DO19 type structure have good potential for high temperature (600°C) applications, due to the thermal stability of the ordered phase and the inherent resistance to recrystallization of these alloys. Five different Ti-Al-Ga alloys consisting of equal atomic percents of aluminum and gallium solute additions up to the stoichiometric composition, Ti3(Al, Ga), were used to study the growth kinetics of the ordered phase and the nature of its interface.The alloys were homogenized in the beta region in a vacuum of about 5×10-7 torr, furnace cooled; reheated in air to 50°C below the alpha transus for hot working. The alloys were subsequently acid cleaned, annealed in vacuo, and cold rolled to about. 050 inch prior to additional homogenization

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Ion Beam Induced Interfacial Reactions in Molybdenum Thin Films on Silicon

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100097466 ◽

1981 ◽

Vol 39 ◽

pp. 162-163

Author(s):

L. J. Chen ◽

L. S. Hung ◽

J. W. Mayer

Keyword(s):

Ion Beam ◽

Chemical Vapor ◽

Interfacial Reactions ◽

Practical Applications ◽

Microelectronic Devices ◽

Recent Emergence ◽

Chemical Vapor Deposited ◽

Atomic Mixing ◽

Silicon Interface ◽

Kinetics Of

When an energetic ion penetrates through an interface between a thin film (of species A) and a substrate (of species B), ion induced atomic mixing may result in an intermixed region (which contains A and B) near the interface. Most ion beam mixing experiments have been directed toward metal-silicon systems, silicide phases are generally obtained, and they are the same as those formed by thermal treatment.Recent emergence of silicide compound as contact material in silicon microelectronic devices is mainly due to the superiority of the silicide-silicon interface in terms of uniformity and thermal stability. It is of great interest to understand the kinetics of the interfacial reactions to provide insights into the nature of ion beam-solid interactions as well as to explore its practical applications in device technology.About 500 Å thick molybdenum was chemical vapor deposited in hydrogen ambient on (001) n-type silicon wafer with substrate temperature maintained at 650-700°C. Samples were supplied by D. M. Brown of General Electric Research & Development Laboratory, Schenectady, NY.

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In situ study of electron beam-induced chemical vapor deposition of Au in an environmental TEM

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100137653 ◽

1995 ◽

Vol 53 ◽

pp. 256-257

Author(s):

J. Drucker ◽

R. Sharma ◽

J. Kouvetakis ◽

K.H.J. Weiss

Keyword(s):

Electron Beam ◽

Chemical Vapor Deposition ◽

Vapor Deposition ◽

Quantum Effect ◽

Line Drawing ◽

Chemical Vapor ◽

Environmental Cell ◽

Engineering Changes ◽

Kinetics Of

Patterning of metals is a key element in the fabrication of integrated microelectronics. For circuit repair and engineering changes constructive lithography, writing techniques, based on electron, ion or photon beam-induced decomposition of precursor molecule and its deposition on top of a structure have gained wide acceptance Recently, scanning probe techniques have been used for line drawing and wire growth of W on a silicon substrate for quantum effect devices. The kinetics of electron beam induced W deposition from WF6 gas has been studied by adsorbing the gas on SiO2 surface and measuring the growth in a TEM for various exposure times. Our environmental cell allows us to control not only electron exposure time but also the gas pressure flow and the temperature. We have studied the growth kinetics of Au Chemical vapor deposition (CVD), in situ, at different temperatures with/without the electron beam on highly clean Si surfaces in an environmental cell fitted inside a TEM column.

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Investigation of irradiation-induced nucleation processes in silicon and germanium

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100137495 ◽

1995 ◽

Vol 53 ◽

pp. 224-225

Author(s):

Harry A. Atwater ◽

C.M. Yang ◽

K.V. Shcheglov

Keyword(s):

Room Temperature ◽

Crystal Size ◽

Initial Distribution ◽

Engineering Control ◽

Size Evolution ◽

Silicon And Germanium ◽

Ge Quantum Dot ◽

And Control ◽

Germanium Quantum Dots ◽

Kinetics Of

Studies of the initial stages of nucleation of silicon and germanium have yielded insights that point the way to achievement of engineering control over crystal size evolution at the nanometer scale. In addition to their importance in understanding fundamental issues in nucleation, these studies are relevant to efforts to (i) control the size distributions of silicon and germanium “quantum dots𠇍, which will in turn enable control of the optical properties of these materials, (ii) and control the kinetics of crystallization of amorphous silicon and germanium films on amorphous insulating substrates so as to, e.g., produce crystalline grains of essentially arbitrary size.Ge quantum dot nanocrystals with average sizes between 2 nm and 9 nm were formed by room temperature ion implantation into SiO2, followed by precipitation during thermal anneals at temperatures between 30°C and 1200°C[1]. Surprisingly, it was found that Ge nanocrystal nucleation occurs at room temperature as shown in Fig. 1, and that subsequent microstructural evolution occurred via coarsening of the initial distribution.

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