Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Controlling low rates of cell differentiation through noise and ultrahigh feedback.

ABSTRACT: Mammalian tissue size is maintained by slow replacement of de-differentiating and dying cells. For adipocytes, key regulators of glucose and lipid metabolism, the renewal rate is only 10% per year. We used computational modeling, quantitative mass spectrometry, and single-cell microscopy to show that cell-to-cell variability, or noise, in protein abundance acts within a network of more than six positive feedbacks to permit pre-adipocytes to differentiate at very low rates. This reconciles two fundamental opposing requirements: High cell-to-cell signal variability is needed to generate very low differentiation rates, whereas low signal variability is needed to prevent differentiated cells from de-differentiating. Higher eukaryotes can thus control low rates of near irreversible cell fate decisions through a balancing act between noise and ultrahigh feedback connectivity.

SUBMITTER: Ahrends R

PROVIDER: S-EPMC4733388 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Controlling low rates of cell differentiation through noise and ultrahigh feedback.

Ahrends Robert R Ota Asuka A Kovary Kyle M KM Kudo Takamasa T Park Byung Ouk BO Teruel Mary N MN

Science (New York, N.Y.) 20140601 6190

Mammalian tissue size is maintained by slow replacement of de-differentiating and dying cells. For adipocytes, key regulators of glucose and lipid metabolism, the renewal rate is only 10% per year. We used computational modeling, quantitative mass spectrometry, and single-cell microscopy to show that cell-to-cell variability, or noise, in protein abundance acts within a network of more than six positive feedbacks to permit pre-adipocytes to differentiate at very low rates. This reconciles two fu ...[more]

PMID: 24948735

Similar Datasets

Ultrahigh dynamic range and low noise figure programmable integrated microwave photonic filter.

Project description:Microwave photonics has adopted a number of important concepts and technologies over the recent pasts, including photonic integration, versatile programmability, and techniques for enhancing key radio frequency performance metrics such as the noise figure and the dynamic range. However, to date, these aspects have not been achieved simultaneously in a single circuit. Here, we report a multi-functional photonic integrated circuit that enables programmable filtering functions with record-high performance. We demonstrate reconfigurable filter functions with record-low noise figure and a RF notch filter with ultra-high dynamic range. We achieve this unique feature using versatile complex spectrum tailoring enabled by an all integrated modulation transformer and a double injection ring resonator as a multi-function optical filtering component. Our work breaks the conventional and fragmented approach of integration, functionality and performance that currently prevents the adoption of integrated MWP systems in real applications.

| S-EPMC9759590 | biostudies-literature

Feedback regulation of proliferation vs. differentiation rates explains the dependence of CD4 T-cell expansion on precursor number.

Project description:The mechanisms regulating clonal expansion and contraction of T cells in response to immunization remain to be identified. A recent study established that there was a log-linear relation between CD4 T-cell precursor number (PN) and factor of expansion (FE), with a slope of ?-0.5 over a range of 3-30,000 precursors per mouse. The results suggested inhibition of precursor expansion either by competition for specific antigen-presenting cells or by the action of other antigen-specific cells in the same microenvironment as the most likely explanation. Several molecular mechanisms potentially accounting for such inhibition were examined and rejected. Here we adopt a previously proposed concept, "feedback-regulated balance of growth and differentiation," and show that it can explain the observed findings. We assume that the most differentiated effectors (or memory cells) limit the growth of less differentiated effectors, locally, by increasing the rate of differentiation of the latter cells in a dose-dependent manner. Consequently, expansion is blocked and reversed after a delay that depends on initial PN, accounting for the dependence of the peak of the response on that number. We present a parsimonious mathematical model capable of reproducing immunization response kinetics. Model definition is achieved in part by requiring consistency with available BrdU-labeling and carboxyfluorescein diacetate succinimidyl ester (CFSE)-dilution data. The calibrated model correctly predicts FE as a function of PN. We conclude that feedback-regulated balance of growth and differentiation, although awaiting definite experimental characterization of the hypothetical cells and molecules involved in regulation, can explain the kinetics of CD4 T-cell responses to antigenic stimulation.

| S-EPMC3044411 | biostudies-literature

Dynamic regulatory network controlling TH17 cell differentiation.

Project description:Despite their importance, the molecular circuits that control the differentiation of naive T cells remain largely unknown. Recent studies that reconstructed regulatory networks in mammalian cells have focused on short-term responses and relied on perturbation-based approaches that cannot be readily applied to primary T cells. Here we combine transcriptional profiling at high temporal resolution, novel computational algorithms, and innovative nanowire-based perturbation tools to systematically derive and experimentally validate a model of the dynamic regulatory network that controls the differentiation of mouse TH17 cells, a proinflammatory T-cell subset that has been implicated in the pathogenesis of multiple autoimmune diseases. The TH17 transcriptional network consists of two self-reinforcing, but mutually antagonistic, modules, with 12 novel regulators, the coupled action of which may be essential for maintaining the balance between TH17 and other CD4(+) T-cell subsets. Our study identifies and validates 39 regulatory factors, embeds them within a comprehensive temporal network and reveals its organizational principles; it also highlights novel drug targets for controlling TH17 cell differentiation.

| S-EPMC3637864 | biostudies-literature

Controlling the emission properties of solution-processed organic distributed feedback lasers through resonator design.

Project description:Surface-emitting distributed feedback (DFB) lasers with both, resonator and active material based on solution-processable polymers, are attractive light sources for a variety of low-cost applications. Besides, the lasers should have competitive characteristics compared to devices based on high-quality inorganic resonators. Here, we report high performing all-solution-processed organic DFB lasers, consisting of water-processed photoresist layers with surface relief gratings located over the active films, whose emission properties can be finely tuned through resonator design. Their laser threshold and efficiency are simultaneously optimized by proper selection of residual resist thickness and grating depth, d. Lowest thresholds and largest efficiencies are obtained when there is no residual layer, while a trade-off between threshold and efficiency is found in relation to d, because both parameters decrease with decreasing d. This behaviour is successfully explained in terms of an overlap factor r, defined to quantify the interaction strength between the grating and the light emitted by the active film and traveling along it, via the evanescent field. It is found that optimal grating depths are in the range 100-130 nm (r ~ 0.5-0.4). Overall, this study provides comprehensive design rules towards an accurate control of the emission properties of the reported lasers.

| S-EPMC6671999 | biostudies-literature

Feedback-based noise management matrix in action.

Project description:BACKGROUND:This article presents the details and findings of a practical implementation of a preliminary model for use in hearing conservation programmes (HCPs) in the mining sector in South Africa. OBJECTIVES:The implementation is based on a previously published model, called feedback-based noise monitoring model (FBNMM), and represents its implementation as a tool of predicting occupational noise-induced hearing loss (ONIHL), as well as monitoring and managing HCPs in the mining sector within the South African context. METHOD:The article, utilising real miners' data, demonstrates this basic static feedback model with its practical applications such as estimating, monitoring and providing quantitative information to aid miners, mining administrators and policymakers in decision-making around HCPs, as recommended in the previous 2019 publication by Moroe et al. This study was conducted in a South African platinum mine. Evidence on the model's sensitivity and practicability in early identification, intervention and management of ONIHL in the workplace is presented. RESULTS:Findings show how the use of the model within an HCP viewed as a complex intervention can allow for early prediction of ONIHL, consequently affording more accurate early intervention as part of preventive audiology within the health and safety goals of mines. CONCLUSION:The feedback-based model should be a useful tool for successful implementation and monitoring of HCPs within South African mines.

| S-EPMC7203224 | biostudies-literature

Cdkn1c drives muscle differentiation through a positive feedback loop with Myod.

Project description:Differentiation often requires conversion of analogue signals to a stable binary output through positive feedback. Hedgehog (Hh) signalling promotes myogenesis in the vertebrate somite, in part by raising the activity of muscle regulatory factors (MRFs) of the Myod family above a threshold. Hh is known to enhance MRF expression. Here we show that Hh is also essential at a second step that increases Myod protein activity, permitting it to promote Myogenin expression. Hh acts by inducing expression of cdkn1c (p57(Kip2)) in slow muscle precursor cells, but neither Hh nor Cdkn1c is required for their cell cycle exit. Cdkn1c co-operates with Myod to drive differentiation of several early zebrafish muscle fibre types. Myod in turn up-regulates cdkn1c, thereby providing a positive feedback loop that switches myogenic cells to terminal differentiation.

| S-EPMC3044464 | biostudies-literature

Noise-driven cell differentiation and the emergence of spatiotemporal patterns.

Project description:The emergence of phenotypic diversity in a population of cells and their arrangement in space and time is one of the most fascinating features of living systems. In fact, understanding multicellularity is unthinkable without explaining the proximate and the ultimate causes of cell differentiation in time and space. Simpler forms of cell differentiation can be found in unicellular organisms, such as bacterial biofilm, where reversible cell differentiation results in phenotypically diverse populations. In this manuscript, we attempt to start with the simple case of reversible nongenetic phenotypic to construct a model of differentiation and pattern formation. Our model, which we refer to as noise-driven differentiation (NDD) model, is an attempt to consider the prevalence of noise in biological systems, alongside what is known about genetic switches and signaling, to create a simple model which generates spatiotemporal patterns from bottom-up. Our simulations indicate that the presence of noise in cells can lead to reversible differentiation and the addition of signaling can create spatiotemporal pattern.

| S-EPMC7182191 | biostudies-literature

Controlling osteogenic stem cell differentiation via soft bioinspired hydrogels.

Project description:Osteogenic differentiation of human mesenchymal stem cells (hMSCs) is guided by various physical and biochemical factors. Among these factors, modulus (i.e., rigidiy) of the ECM has gained significant attention as a physical osteoinductive signal that can contribute to endochondral ossification of a cartilaginous skeletal template. However, MSCs also participate in intramembranous bone formation, which occurs de novo from within or on a more compliant tissue environment. To further understand the role of the matrix interactions in this process, we evaluated osteogenic differentiation of hMSCs cultured on low moduli (102, 390 or 970 Pa) poly(N-isopropylacrylamide) (p(NIPAAm)) based semi-interpenetrating networks (sIPN) modified with the integrin engaging peptide bsp-RGD(15) (0, 105 or 210 µM). Cell adhesion, proliferation, and osteogenic differentiation of hMSCs, as measured by alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), bone sialoprotein-2 (iBSP), and osteocalcien (OCN) protein expression, was highest on substrates with the highest modulus and peptide concentrations. However, within this range of substrate stiffness, many osteogenic cellular functions were enhanced by increasing either the modulus or the peptide density. These findings suggest that within a compliant and low modulus substrate, a high affinity adhesive ligand serves as a substitute for a rigid matrix to foster osteogenic differentiation.

| S-EPMC4060996 | biostudies-literature

Cell shape regulation through mechanosensory feedback control.

Project description:Cells undergo controlled changes in morphology in response to intracellular and extracellular signals. These changes require a means for sensing and interpreting the signalling cues, for generating the forces that act on the cell's physical material, and a control system to regulate this process. Experiments on Dictyostelium amoebae have shown that force-generating proteins can localize in response to external mechanical perturbations. This mechanosensing, and the ensuing mechanical feedback, plays an important role in minimizing the effect of mechanical disturbances in the course of changes in cell shape, especially during cell division, and likely in other contexts, such as during three-dimensional migration. Owing to the complexity of the feedback system, which couples mechanical and biochemical signals involved in shape regulation, theoretical approaches can guide further investigation by providing insights that are difficult to decipher experimentally. Here, we present a computational model that explains the different mechanosensory and mechanoresponsive behaviours observed in Dictyostelium cells. The model features a multiscale description of myosin II bipolar thick filament assembly that includes cooperative and force-dependent myosin-actin binding, and identifies the feedback mechanisms hidden in the observed mechanoresponsive behaviours of Dictyostelium cells during micropipette aspiration experiments. These feedbacks provide a mechanistic explanation of cellular retraction and hence cell shape regulation.

| S-EPMC4535415 | biostudies-literature

Ultrahigh-Q metallic nanocavity resonances with externally-amplified intracavity feedback.

Project description:We propose a mechanism of ultrahigh-Q metallic nanocavity resonances that involves an efficient loss-compensation scheme favorable for room-temperature operation. We theoretically show that surface plasmon-polaritons excited on the entrance and exit interfaces of a metallic nanocavity array efficiently transfer external optical gain to the cavity modes by inducing resonantly-amplified intracavity feedback. Surprisingly, the modal gain in the nanocavity with the externally amplified feedback is inversely proportional to the cavity length as opposed to conventional optical cavity amplifiers requiring longer cavities for higher optical gain. Utilizing this effect, we numerically demonstrate room-temperature nanocavity resonance Q-factor exceeding 10(4) in a 25-nm-wide silver nanoslit array. The proposed mechanism provides a highly efficient plasmonic amplification process particularly for subwavelength plasmonic cavities which are essential components in active nanoplasmonic devices.

| S-EPMC4237986 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data