Spatial transcriptomics reveals a conserved segment polarity program that governs muscle patterning in Nematostella vectensis
Ontology highlight
ABSTRACT:
ORGANISM(S): Nematostella vectensis
PROVIDER: GSE173786 | GEO | 2023/06/12
REPOSITORIES: GEO
Similar Datasets
Project description:MicroRNAs of bilaterian animals undergo posttranscriptional modifications such as methylation, tailing and trimming that regulate miRNA stability and function. To gain insight on the evolution of miRNA posttranscriptional modification, we studied regulation of miRNA stability by methylation in the sea anemone Nematostella vectensis, a representative of Cnidaria, the sister group of Bilateria.
2017-08-15 | GSE94526 | GEO
Project description:The WRAMP structure is a protein network associated with tail-end actomyosin contractility, membrane retraction, and directional persistence during cell migration. A marker of WRAMP structures is melanoma cell adhesion molecule (MCAM) which dynamically polarizes to the cell rear. However, factors that mediate MCAM polarization are still unknown. In this study, BioID using MCAM as bait identifies the ERM family proteins, moesin, ezrin, and radixin, as WRAMP structure components. We also present a novel image analysis pipeline, Protein Polarity by Percentile (“3P”), which classifies protein polarization using machine learning and facilitates quantitative analysis. Using 3P, we find that depletion of moesin, and to a lesser extent ezrin, decreases the proportion of cells with polarized MCAM. Furthermore, although co-polarized MCAM and ERM proteins show high spatial overlap, 3P identifies subpopulations with ERM proteins closer to the cell periphery. Live-cell imaging confirms that MCAM and ERM protein polarization is tightly coordinated, but ERM proteins enrich at the cell edge first. Finally, deletion of a juxtamembrane segment in MCAM previously shown to promote ERM protein interactions impedes MCAM polarization. Our findings highlight the requirement for ERM proteins in recruitment of MCAM to WRAMP structures and an advanced computational tool to characterize protein polarization.
2024-05-22 | PXD047722 | Pride
Project description:Differentiation of monolayered epithelia is characterized by the formation of a basoapical polarity axis, except during the early stages of cancer development. Using mammary glandular structures (acini) produced in a three-dimensional cell culture system we have demonstrated that, in order for mammary epithelial cells to exit quiescence and enter the cell cycle, acini have to lose apical polarity. In order to identify the genes dependent on apical polarity that could control cell quiescence, and possibly other aspects of tissue homeostasis, we have used Affymetrix technology microarray analysis of the 22,277 features/genes of the Human Genome U133A 2.0 array Chip in apically polarized and non-polarized breast epithelial acinar cells in three-dimensional culture. Genes commonly down-regulated in two treatments that altered apical polarity compared to control were considered to be dependent on apical polarity status for their transcription. Apically polarized (Control) and two different populations of non-polarized human mammary epithelial cells (18-alpha-glycyrrhetinic acid =AGA, and 5-aza-2'-deoxycytidine =Aza) were used for microarray analysis containing four biological replicates (1-4) for each treatment. The two treatments that cause loss of apical polarity were compared to reference apically polarized control samples using two different statistical analysis methods (FDR and HolmM-bM-^@M-^Ys).
2012-02-29 | E-GEOD-35165 | biostudies-arrayexpress
Project description:Early neuronal development is a well-coordinated process in which neuronal stem cells differentiate into polarized neurons. This process has been well studied in classical non-human model systems, but to what extent this is recapitulated in human neurons remains unclear. To study neuronal polarization in human neurons, we cultured human iPSC-derived neurons, characterized early developmental stages, measured electrophysiological responses, and systematically profiled transcriptomic and proteomic dynamics during these steps. We found extensive remodeling of the neuron transcriptome and proteome, with altered mRNA expression of ~1,100 genes and different expression profiles of ~1,500 proteins during neuronal differentiation and polarization. We also identified a distinct stage in axon development marked by an increase in microtubule remodeling and apparent relocation of the axon initial segment from the distal to proximal axon. Our comprehensive characterization and quantitative map of transcriptome and proteome dynamics provides a solid framework for studying polarization in human neurons.
2020-11-17 | PXD020227 | Pride
Project description:In response to polarization cues, cultured Caco-2 cells, a human colon adenocarcinoma-derived cell line, form a polarized epithelium resembling normal enterocytes. We investigated potential signaling mechanisms activated by Caco-2 cells that might trigger the genome-wide transcriptional reprogramming that accompanies polarization (Saaf et al, submitted-I). cDNA microarrays were used to compare the transcriptional profile of Caco-2 polarization to the gene expression profiles of normal human colon and colon tumors. The transcript profile of proliferating, non-polarized Caco-2 cells has striking parallels to the gene expression profile of human colon cancer in vivo. However, as Caco-2 cells develop polarity, the gene expression profile shifts to one more closely resembling that of normal colon tissue, suggesting that the underlying regulatory mechanisms that mediate Caco-2 cell polarization are similar to those that occur during in vivo enterocyte differentiation. We show that transcriptional re-programming of Caco-2 cells during development of cell polarity occurs in the context of signaling pathways that are regulated in a manner that is remarkably similar to those in normal intestinal development. For example, transcriptional targets of the Wnt pathway are tightly regulated during Caco-2 cell polarization, mimicking the gradient of Wnt-mediated transcription in the crypt (high expression) to villus (low expression) axis in human intestine. However, Caco-2 cells lack full-length APC necessary for normal Wnt-regulated degradation of beta-catenin. Biochemical analysis indicates that regulation of the Wnt pathway occurs in the nucleus at the level of activation of target genes by the beta-catenin-TCF complex, revealing a novel additional mechanism by which intestinal cells may regulate Wnt signaling during their maturation. In addition, other signaling pathways including Notch, BMP, Hedgehog, and growth factor, were temporally regulated during Caco-2 cell polarization. Surprisingly, modulation of these signaling pathways in Caco-2 cells occurs in the absence of morphogen gradients and interactions with stromal cells characteristic of enterocyte differentiation in situ. This dataset contains gene expression profiles of 9 normal colon samples and 15 colon tumor samples. Samples of tumor and normal colon mucosa were collected from colon cancer resection from Department of Surgery, Queen Mary Hospital University of Hong Kong. Tissue was frozen in liquid nitrogen within 30 min of resection. Nonneoplastic mucosa from colon was dissected free of muscle and histologically confirmed to be tumor free by frozen section. Total RNA was extracted using Trizol (Invitrogen, Carlsbad, CA) from each tissue sample and processed for microarray hybridization. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Disease State: Tumor/Normal colon samples Using regression correlation
2007-08-17 | E-GEOD-7466 | biostudies-arrayexpress
Project description:To get insights into domain organization and functioning of the Danio rerio major α/β-globin locus (Mα/βGL), we have characterized profiles of histone H3 panacetylation across this locus in erythrocytes of adult fish and 18 dpf larvas. To identify enriched domains in our ChipSeq data we used our original protocol and peak caller MACS2. Histone acetylation profiles of Mα/βGL for adult and embryo cells reveal a breaking point in upstream region of the first embryo-larval gene βe1.There are two sub-segments of acetylation: sub-segment to the left of βe1 harbors adult-specific globin genes and is acetylated only in adult cells. Embryo sub-segment contains embryo-larval globin genes and is located to the right of βe1 gene. Acetylation in this subsegment was detected only in 18 dpf larva. Acetylation profile in adult subs-egment possess largest acetylation domain which covers two pairs of adult-stage globins: αa1, and βa1. High acetylation level in this domain well correlates with high expression level observed for these 4 genes in adult erythrocyte. Pattern of H3 panacetylation in 18 dpf larval erythrocytes differs strikingly from that for adult cells. Embryo-larval segment is fragmented in small domains co-located with gene bodies with gaps in intergenic regions. Adult subsegment in adult cells contains strong acetylation domain that cover 4 globin genes along with a part of intergenic regions and few smaller domains. Alternative stage-specific acetylation of subdomains and different pattern of embryonic-larval and adult domain acetylation strongly support the hypothesis of deep structural and functional segregation of stage-specific subdomains within Mα/βGL locus in zebrafish.
2017-01-01 | GSE86548 | GEO
Project description:Hepatocytes are highly polarized epithelia. Loss of hepatocyte polarity is associated with various liver diseases, including cholestasis. However, the molecular underpinnings of hepatocyte polarization remain poorly understood. Previously, we have shown that loss of β-catenin at adherens junctions (AJs) is compensated by β-catenin and dual loss of both catenins in dual knockouts (DKO) in mice liver leads to progressive intrahepatic cholestasis. However, the clinical relevance of this observation, and further phenotypic characterization of the phenotype, is important. Here, we identify simultaneous loss of β- and γ-catenin in a subset of liver samples from patients of progressive familial intrahepatic cholestasis and primary sclerosing cholangitis. Hepatocytes in DKO mice exhibited defect in apical-basolateral localization of polarity proteins, impaired bile canaliculi formation, and loss of microvilli. Loss of polarity in DKO livers manifested as epithelial-to-mesenchymal transition, increased hepatocyte proliferation, and suppression of hepatocyte differentiation, which was associated with up-regulation of TGFβ signaling and repression of Hnf4α expression and activity. In conclusion, concomitant loss of the two catenins in the liver may be playing a pathogenic role in subsets of cholangiopathies. Our findings also support a previously unknown role β- and γ-catenin in the maintenance of hepatocyte polarity. Improved understanding of the regulation of hepatocyte polarization processes by β and γ-catenin could potentially benefit development of new therapies for cholestasis.
2021-02-14 | GSE166087 | GEO
Project description:This spatio-temporal model explores tissue polarity re-organization during planarian double-head formation upon regeneration with beta-catenin-1 RNAi treatment. Initial conditions for A and M polarity fields are chosen near the wild type pattern and the first 100 time steps are used to establish the typical wild type splay pattern. The induction of the ectopic head occurs at time-step 100 (interpreted as tail amputation time) at the position where the former tail was (right end), subsequently affects the nearby tissue with some lag and then re-polarizes the posterior half of the tissue from time-step 200 onward. Of these polarity fields, A represents the anterior-posterior polarization system provided by the core PCP pathway, M represents the medio-lateral polarization system provided by the Ft/Ds pathway and P represents the resulting superimposed and normalized polarization. P can be compared to the observable polarity data of ciliary rootlets. This simulation reproduces Figure 4D of the referenced paper. Parameter values correspond to the beta-catenin-1(RNAi) pattern as given in Table S2 of the referenced paper. The model file is in MorpheusML format and can be opened in the free, open-source multicellular modeling software Morpheus (https://morpheus.gitlab.io) to simulate the time course (movie) of the spatio-temporal dynamics.
2021-10-06 | MODEL2110050001 | BioModels
Project description:Early neuronal development is a well-coordinated process in which neuronal stem cells differentiate into polarized neurons. This process has been well studied in classical non-human model systems, but to what extent this is recapitulated in human neurons remains unclear. To study neuronal polarization in human neurons, we cultured human iPSC-derived neurons, characterized early developmental stages, measured electrophysiological responses, and systematically profiled transcriptomic and proteomic dynamics during these steps. We found extensive remodeling of the neuron transcriptome and proteome, with altered mRNA expression of ~1,100 genes and different expression profiles of ~1,500 proteins during neuronal differentiation and polarization. We also identified a distinct stage in axon development marked by an increase in microtubule remodeling and apparent relocation of the axon initial segment from the distal to proximal axon. Our comprehensive characterization and quantitative map of transcriptome and proteome dynamics provides a solid framework for studying polarization in human neurons.
2020-07-28 | GSE155212 | GEO
Project description:The model explores the establishment and stability of the wildtype polarity pattern in planarian flatworms. Initial conditions for A and M fields are chosen as arbitrarily perturbed to demonstrate stability of the wild type pattern. A represents the A/P polarization system, M represents the M/L polarization system and P represents the resulting superimposed and normalized polarization. P can be compared to the measured polarity data of ciliary rootlets. This simulation reproduces Figure 4C of the referenced paper. Parameter values correspond to the wild type pattern (control) as given in Table S2 of the referenced paper. The model file is in MorpheusML format and can be opened in the free, open-source multicellular modeling software Morpheus (https://morpheus.gitlab.io) to simulate the time course (movie) of the spatio-temporal dynamics.
2021-10-05 | MODEL2107170001 | BioModels