Zebrafish chemical compound screen uncovers inducers of skeletal muscle engraftment across species
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA601746 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10903528_1.fastq.gz | Fastqsanger.gz | |||
| SRR10903528_2.fastq.gz | Fastqsanger.gz | |||
| SRR10903529_1.fastq.gz | Fastqsanger.gz | |||
| SRR10903529_2.fastq.gz | Fastqsanger.gz | |||
| SRR10903530_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 36 |
Similar Datasets
Project description:Stem cell transplantation presents a potentially curative strategy for genetic disorders of skeletal muscle, but the application of this approach has been limited due to the deleterious effects of cell expansion in vitro and poor engraftment efficiency. In an effort to overcome this hurdle, we sought to identify molecular signals that enhance the myogenic activity of cultured muscle progenitors. Here, we report the development and application of a cross-species small molecule screening platform employing zebrafish and mouse, which enables rapid, direct evaluation of the effects of chemical compounds on the engraftment of transplanted muscle precursor cells. Using this system, we screened a library of bioactive lipids to identify those that could increase myogenic engraftment in zebrafish and mice. These efforts identified two lipids, lysophosphatidic acid (LPA) and niflumic acid (NFA), both linked to activation of intracellular calcium ion flux, which showed conserved, dose-dependent and synergistic effects in promoting muscle engraftment across these vertebrate species.
2023-01-16 | GSE143801 | GEO
Project description:Haematopoietic stem and progenitor cell (HSPC) transplant is a widely used treatment for life-threatening conditions including leukemia; however, the molecular mechanisms regulating HSPC engraftment of the recipient niche remain incompletely understood. Here, we developed a competitive HSPC transplant method in adult zebrafish, using in vivo imaging as a non-invasive readout. We used this system to conduct a chemical screen and identified epoxyeicosatrienoic acids (EET) as a family of lipids that enhance HSPC engraftment. EETs’ pro-haematopoietic effects are conserved in the developing zebrafish, where this molecule promotes HSPC specification through activating a unique AP-1/runx1 transcription program autonomous to the haemogenic endothelium. This effect requires the activation of PI3K pathway, specifically PI3Kg. In adult HSPCs, EETs induce transcriptional programs including AP-1 activation, modulating multiple cellular processes, such as migration, to promote engraftment. Finally, we demonstrated that the EET effects on enhancing HSPC homing and engraftment are conserved in mammals. Our study established a novel method to explore the molecular mechanisms of HSPC engraftment, and discovered a previously unrecognized, evolutionarily conserved pathway regulating multiple haematopoietic generation and regeneration processes. EETs may have clinical application in marrow or cord blood transplantation.
2015-07-13 | GSE66767 | GEO
Project description:During the bloodstream stage of the Trypanosoma brucei lifecycle, the parasite exists as the proliferative slender-form or the non-proliferative, transmissible, stumpy-form. The transition from the slender to stumpy-form is stimulated by a density-dependent mechanism and is important in infection dynamics, ordered antigenic variation and disease transmissibility. Here, we use a monomorphic reporter cell line in a whole-cell fluorescence-based assay to screen over 6000 small molecules from a kinase-focussed compound library for their ability to induce stumpy-like formation in a high-throughput screening programme. This identified one compound able to induce modest, yet specific, changes in gene expression indicative of a partial differentiation to stumpy forms. This not only provides a potential tool for the further understanding of stumpy formation, but also demonstrates the use of high throughput screening in the identification of compounds able to induce specific phenotypes, such as differentiation, in African trypanosomes. Examination of gene expression in response to treatment with DDD00015314.
2014-01-21 | E-GEOD-46483 | biostudies-arrayexpress
Project description:During the bloodstream stage of the Trypanosoma brucei lifecycle, the parasite exists as the proliferative slender-form or the non-proliferative, transmissible, stumpy-form. The transition from the slender to stumpy-form is stimulated by a density-dependent mechanism and is important in infection dynamics, ordered antigenic variation and disease transmissibility. Here, we use a monomorphic reporter cell line in a whole-cell fluorescence-based assay to screen over 6000 small molecules from a kinase-focussed compound library for their ability to induce stumpy-like formation in a high-throughput screening programme. This identified one compound able to induce modest, yet specific, changes in gene expression indicative of a partial differentiation to stumpy forms. This not only provides a potential tool for the further understanding of stumpy formation, but also demonstrates the use of high throughput screening in the identification of compounds able to induce specific phenotypes, such as differentiation, in African trypanosomes.
2014-01-21 | GSE46483 | GEO
Project description:K. phaffii strain BSYBG10 with multiple inducers, sampled after 3h
| PRJEB58889 | ENA
Project description:We performed proteomic profiling of 88 HNSCC patients to investigate the molecular phenotype associated with engraftment. We complemented the analysis with HNSC and normal oral epithelial cell lines.
2024-04-09 | MSV000094507 | MassIVE
Project description:Natural products (NP) encompass a rich source of bioactive chemical entities. Hence, NPs-derived compounds represent the majority of drugs currently approved to treat cancer. Here, we used human cancer stem cells (CSCs) in a chemical genomics campaign with NP chemical space to interrogate extracts from diverse strains of actinomycete for anti-cancer properties. We identified a compound (SCCRI025044), capable of selectively inhibiting human CSC function vs. normal stem cell (SC) counterparts. Biochemical and molecular studies revealed that SCCRI025044 exerts inhibition on human CSCs through the small ubiquitin-like modifier (SUMO) cascade, found to be hyperactive in human CSCs. SCCRI025044 impedes SUMOylation pathway via direct targeting of the SAE1/2 complex. Treatment of patient-derived CSCs resulted in reduced levels of SUMOylated proteins and suppression of progenitor and stem cell capacity measured in vitro and in vivo. Our study overcomes a barrier in chemically inhibiting oncogenic SUMOylation activity and uncovers a unique role for SAE2 in human CSC biology.
2023-10-01 | GSE160551 | GEO
Project description:The application of gene expression profiling technology to examine multiple genes and signaling pathways simultaneously promises a significant advance in understanding toxic mechanisms to ultimately aid in protection of public health. Public and private efforts in the new field of toxicogenomics are focused on populating databases with gene expression profiles of compounds where toxicological and pathological endpoints are well characterized. The validity and utility of a toxicogenomics is dependent on whether gene expression profiles that correspond to different chemicals can be distinguished. The principal hypothesis underlying a toxicogenomic or pharmacogenomic strategy is that chemical-specific patterns of altered gene expression will be revealed using high-density microarray analysis of tissues from exposed organisms. Analyses of these patterns should allow classification of toxicants and provide important mechanistic insights. This report provides a verification of this hypothesis. Patterns of gene expression corresponding to liver tissue derived from chemically exposed rats revealed similarity in gene expression profiles between animals treated with different agents from a common class of compounds, peroxisome proliferators [clofibrate (ethyl-p-chlorophenoxyisobutyrate), Wyeth 14,643 ([4-chloro-6(2,3-xylidino)-2-pyrimidinylthio]acetic acid), and gemfibrozil (5-2[2,5-dimethylphenoxy]2-2-dimethylpentanoic acid)], but a very distinct gene expression profile was produced using a compound from another class, enzyme inducers (phenobarbital). Keywords: other
2002-11-20 | GSE95 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE32727: EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors [human] GSE32904: EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors [mouse] Refer to individual Series
2012-07-23 | E-GEOD-32905 | biostudies-arrayexpress
Project description:The compound (O4I3) showed a remarkable OCT4 induction, which at least in part, is due to the inhibition of H3K4-specific lysine demethylase (KDM5, also known as JARID1). Experiments demonstrated that KDM5A, serves as a reprogramming barrier via interference with the enrichment of H3K4Me3 at the OCT4 promoter. Thus, our results introduce a new class of KDM5 chemical inhibitors and provide further insight into the pluripotency-related properties of KDM5-family members.
2018-12-12 | GSE123668 | GEO