Glycolytic flux controls retinal progenitor cell differentiation via regulating Wnt signaling DOI Open Access

Joseph Hanna,

Yacine Touahri,

Alissa Pak

и другие.

Опубликована: Окт. 4, 2024

Metabolic pathways are remodeled in response to energy and other homeostatic demands dynamically regulated during embryonic development, suggestive of a role guiding cellular differentiation. Here, we show that glycolytic flux is required sufficient bias multipotent retinal progenitor cells (RPCs) acquire rod photoreceptor fate the murine retina. In an RPC-specific conditional knock-out Phosphatase tensin homolog ( Pten- cKO) gain-of-function dominant active PFKB3 (cyto ), gene expression activity elevated, correlating with precocious differentiation outer segment maturation. Conversely, inhibition explants, achieved either 2-deoxy-d-glucose, competitive inhibitor glucose metabolism, by lowering media pH, which disables PKM2, rate-limiting enzyme, or inhibiting lactate/H + symporters, lowers intracellular suppresses RPC proliferation Mechanistically, Wnt signaling, top-upregulated pathway cKO retinas, glycolysis-dependent pathway. Pharmacological genetic perturbation signaling using Ctnnb1- phenocopies inhibition, suppressing proliferation, Thus, developmental rewiring modulates drive maturation, instructive may be exploited therapeutically for cell replacement strategies.

Язык: Английский

On the reversibility of amyloid fibril formation DOI Creative Commons
Tinna Pálmadóttir,

Josef Getachew,

Lei Ortigosa-Pascual

и другие.

Biophysics Reviews, Год журнала: 2025, Номер 6(1)

Опубликована: Янв. 29, 2025

Amyloids are elongated supramolecular protein self-assemblies. Their formation is a non-covalent assembly process and as such fully reversible. Amyloid associated with several neurodegenerative diseases, the reversibility key to maintaining healthy state. Reversibility also performance of fibril-based biomaterials functional amyloids. The can be observed by range spectroscopic, calorimetric, or surface-based techniques using starting state either supersaturated monomer solution diluted fibrils. has characteristics phase transition, we provide some basic formalism for derivation solubility/critical concentration. We discuss conditions under which dissociation amyloids may so slow that viewed practically irreversible, example, because it relative experimental time frame system at hand contains source constant addition.

Язык: Английский

Процитировано

1
Compartmentalization of multiple metabolic enzymes and their preparation in vitro and in cellulo DOI

Sayoko Ito‐Harashima,

Natsuko Miura

Biochimica et Biophysica Acta (BBA) - General Subjects, Год журнала: 2025, Номер unknown, С. 130787 - 130787

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

1
Toward Design Principles for Biomolecular Condensates for Metabolic Pathways DOI Creative Commons
Alain A.M. André,

Nikita Rehnberg,

Ankush Garg

и другие.

Advanced Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

Abstract Biology uses membrane‐less organelles or biomolecular condensates as dynamic reaction compartments that can form dissolve to regulate biochemical pathways. This has led a flurry of research aiming design new synthetic function crucibles for enzymes and cascades in biotechnology. The mechanisms by which condensate enhance multistep processes including mass action, tuning the chemical environment, scaffolding metabolic channelling is reviewed. These are not inherently beneficial rate enzymatic but also inhibit reaction. Similarly, some aspects likely intrinsically inhibitory retardation diffusion, where net effect will be trade‐off between stimulatory effects. It discussed generalizable conclusions drawn so far how close it principles enzyme microbial cell factories reactions enhanced type suited

Язык: Английский

Процитировано

1
Systematic Comparison of Commercial Uranyl‐Alternative Stains for Negative‐ and Positive‐Staining Transmission Electron Microscopy of Organic Specimens DOI Creative Commons
Vera M. Kissling,

Stephanie Eitner,

Davide Bottone

и другие.

Advanced Healthcare Materials, Год журнала: 2025, Номер unknown

Опубликована: Апрель 29, 2025

Abstract Negative‐ and positive‐staining transmission electron microscopy (ns/psTEM) is a cornerstone of research diagnostics, enabling nanometer‐resolution analysis organic specimens from nanoparticles to cells without requiring costly cryo‐equipment. For nearly 70 years, uranyl salts like acetate (UA) have been the gold‐standard ns/psTEM‐stains. However, mounting safety concerns due their high toxicity radioactivity led stricter regulations expensive licensing requirements. Consequently, there an urgent global demand for safer, more sustainable stains that deliver uranyl‐comparable, high‐quality ns/psTEM. Here, commercially available stain‐alternatives UranyLess, UAR, UA‐Zero, PTA, STAIN 77, Nano‐W, NanoVan, lead citrate are systematically assessed against UA. The evaluated regarding contrast, resolution, stain‐distribution, ease‐of‐use in ns/psTEM across diverse sample set, including polymethylmethacrylate‐nanoplastics, phosphatidylcholine‐liposomes, Influenza‐A viruses, globular ferritin, fibrillar pyruvate kinase amyloids, human lung‐carcinoma cell‐sections. It shown this variety samples, ready‐to‐use uranyl‐alternative with comparable or even superior ns/psTEM‐performance UA using efficient staining‐protocol. Furthermore, GUIDE4U tool developed fast identification appropriate uranyl‐replacements each interest, saving ns/psTEM‐users time costs while ensuring excellent staining results ultrastructural analysis, thereby further catalyzing use safer stains.

Язык: Английский

Процитировано

0
Glycolytic flux controls retinal progenitor cell differentiation via regulating Wnt signaling DOI Open Access

Joseph Hanna,

Yacine Touahri,

Alissa Pak

и другие.

Опубликована: Май 14, 2025

Abstract Metabolic pathways are remodeled in response to energy and other homeostatic demands dynamically regulated during embryonic development, suggesting a role guiding cellular differentiation. Here, we show that glycolytic flux is required sufficient bias multipotent retinal progenitor cells (RPCs) acquire rod photoreceptor fate the murine retina. In an RPC-specific conditional knock-out of Phosphatase tensin homolog (Pten-cKO) gain-of-function dominant active PFKB3 (cytoPFKB3), gene expression activity elevated, correlating with precocious differentiation outer segment maturation. Conversely, inhibition explants, achieved either 2-deoxy-d-glucose, competitive inhibitor glucose metabolism, by lowering media pH, which disables PKM2, rate-limiting enzyme, or inhibiting lactate/H+ symporters, lowers intracellular suppresses RPC proliferation Mechanistically, Wnt signaling, top-upregulated pathway Pten-cKO retinas, glycolysis-dependent pathway. Pharmacological genetic perturbation signaling using Ctnnb1-cKO phenocopies inhibition, suppressing proliferation, Thus, developmental rewiring modulates drive maturation, instructive may be exploited therapeutically for cell replacement strategies.

Язык: Английский

Процитировано

0
Oxidation-sensitive cysteines drive IL-38 amyloid formation DOI Creative Commons
Alejandro Díaz-Barreiro, Gea Cereghetti, Francisco G. Ortega

и другие.

Cell Reports, Год журнала: 2024, Номер 43(11), С. 114940 - 114940

Опубликована: Ноя. 1, 2024

Interleukin (IL)-1 family cytokines are essential for host defense at epithelial barriers. The IL-1 member IL-33 was recently linked to stress granules (SGs). Formation of SGs and other biomolecular condensates is promoted by proteins containing low-complexity regions (LCRs). Computational analysis predicts LCRs in six the 11 members. Among these, IL-38 contains a long LCR including two amyloid cores. localizes intracellular keratinocytes under oxidative (OS) forms OS-induced aggregates cells vitro. Interestingly, soluble aggregated released from an exosome-enriched extracellular vesicle fraction. Disulfide-bond mapping, silico modeling, mutational suggest that oxidation-sensitive cysteines act as redox switches alter conformation promote its aggregation. Finally, presence human epidermis facing environmental OS suggests oxidation-induced amyloidogenesis, intrinsic property IL-38, supports barrier function.

Язык: Английский

Процитировано

2
Glycolytic flux controls retinal progenitor cell differentiation via regulating Wnt signaling DOI Creative Commons

Joseph Hanna,

Yacine Touahri,

Alissa Pak

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 13, 2024

ABSTRACT Metabolic pathways are remodeled in response to energy and other homeostatic demands dynamically regulated during embryonic development, suggestive of a role guiding cellular differentiation. Here, we show that glycolytic flux is required sufficient bias multipotent retinal progenitor cells (RPCs) acquire rod photoreceptor fate the murine retina. In an RPC-specific conditional knock-out Phosphatase tensin homolog ( Pten- cKO) gain-of-function dominant active PFKB3 (cyto ), gene expression activity elevated, correlating with precocious differentiation outer segment maturation. Conversely, inhibition explants, achieved either 2-deoxy-d-glucose, competitive inhibitor glucose metabolism, by lowering media pH, which disables PKM2, rate-limiting enzyme, or inhibiting lactate/H + symporters, lowers intracellular suppresses RPC proliferation Mechanistically, Wnt signaling, top-upregulated pathway cKO retinas, glycolysis-dependent pathway. Pharmacological genetic perturbation signaling using Ctnnb1- phenocopies inhibition, suppressing proliferation, Thus, developmental rewiring modulates drive maturation, instructive may be exploited therapeutically for cell replacement strategies. IMPACT STATEMENT Transgenic pharmacological approaches reveal elevations have promoting maturation via activation signaling.

Язык: Английский

Процитировано

0
Glycolytic flux controls retinal progenitor cell differentiation via regulating Wnt signaling DOI Open Access

Joseph Hanna,

Yacine Touahri,

Alissa Pak

и другие.

Опубликована: Окт. 4, 2024

Metabolic pathways are remodeled in response to energy and other homeostatic demands dynamically regulated during embryonic development, suggestive of a role guiding cellular differentiation. Here, we show that glycolytic flux is required sufficient bias multipotent retinal progenitor cells (RPCs) acquire rod photoreceptor fate the murine retina. In an RPC-specific conditional knock-out Phosphatase tensin homolog ( Pten- cKO) gain-of-function dominant active PFKB3 (cyto ), gene expression activity elevated, correlating with precocious differentiation outer segment maturation. Conversely, inhibition explants, achieved either 2-deoxy-d-glucose, competitive inhibitor glucose metabolism, by lowering media pH, which disables PKM2, rate-limiting enzyme, or inhibiting lactate/H + symporters, lowers intracellular suppresses RPC proliferation Mechanistically, Wnt signaling, top-upregulated pathway cKO retinas, glycolysis-dependent pathway. Pharmacological genetic perturbation signaling using Ctnnb1- phenocopies inhibition, suppressing proliferation, Thus, developmental rewiring modulates drive maturation, instructive may be exploited therapeutically for cell replacement strategies.

Язык: Английский

Процитировано

0
Glycolytic flux controls retinal progenitor cell differentiation via regulating Wnt signaling DOI Open Access

Joseph Hanna,

Yacine Touahri,

Alissa Pak

и другие.

Опубликована: Окт. 4, 2024

Metabolic pathways are remodeled in response to energy and other homeostatic demands dynamically regulated during embryonic development, suggestive of a role guiding cellular differentiation. Here, we show that glycolytic flux is required sufficient bias multipotent retinal progenitor cells (RPCs) acquire rod photoreceptor fate the murine retina. In an RPC-specific conditional knock-out Phosphatase tensin homolog ( Pten- cKO) gain-of-function dominant active PFKB3 (cyto ), gene expression activity elevated, correlating with precocious differentiation outer segment maturation. Conversely, inhibition explants, achieved either 2-deoxy-d-glucose, competitive inhibitor glucose metabolism, by lowering media pH, which disables PKM2, rate-limiting enzyme, or inhibiting lactate/H + symporters, lowers intracellular suppresses RPC proliferation Mechanistically, Wnt signaling, top-upregulated pathway cKO retinas, glycolysis-dependent pathway. Pharmacological genetic perturbation signaling using Ctnnb1- phenocopies inhibition, suppressing proliferation, Thus, developmental rewiring modulates drive maturation, instructive may be exploited therapeutically for cell replacement strategies.

Язык: Английский

Процитировано

0