Apical-basal polarity drives pancreatic alpha/beta cell fate allocation
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ABSTRACT:
PROVIDER: PRJNA930460 | ENA |
REPOSITORIES: ENA
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Project description:Fate commitment is a sum of unique intrinsic properties and extrinsic cues received by a progenitor/stem cell. The knowledge of intrinsic properties, such as transcription, is extensive, whereas much less is known about how they are regulated by extrinsic cues, such as cell-cell and cell-extracellular matrix (ECM) interactions. We demonstrated that differential cell-cell adhesion controls the fate of multipotent pancreatic progenitors by dictating their migration to the tip and trunk niches where they are exposed to specific fate-inducing cues. Within the trunk each Neurogenin 3+ (Neurog3+) endocrine progenitor can give rise to all five pancreatic islet hormone-producing endocrine cells. Forced exiting of Neurog3+ from the polarize luminal epithelium through conditional ablation of p120ctn or Ecad in Neurog3+ cells shift their differentiation towards alpha cells at the expense of beta cells. Based on these findings we hypothesized that cell adhesion and cell polarity might be linked to the fate decision of Neurog3+ cells into the alpha and beta cell lineages. Here, we show pancreatic endocrine progenitor cell-cell adhesion is linked to apical-basal polarity and cell fate, and disruption of apical-basal polarity in the developing mouse pancreas alters endocrine cell specification. Futhermore, apical-basally polarized human endocrine progenitors are primed to become beta cells. Finally, single-cell RNA sequencing reveals beta-like transcriptional signatures and differentiation propensities in polarized endocrine progenitors.
2025-01-01 | GSE224286 | GEO
Project description:The epiblast is the first cell type that forms apical-basal polarity de novo as the mouse embryo implants into the maternal uterus, while the extraembryonic neighbours of the epiblast - trophectoderm and primitive endoderm - retain their pre-established polarity beyond implantation [1]; however, it is still unclear how the epiblast establishes apical-basal polarity de novo. Here, we focused on Rap1 signaling pathway, which is activated during the transition of the epiblast from the naïve to primed state of pluripotency during implantation [2]. Through the preestablished in vitro three-dimensional culture system [3], genetic knockouts and proximity-biotinylation analyses, we found that Rap1 integrates multiple signals that contribute to de novo formation of apical-basal polarity. Importantly, formation of apical-basal polarity in the epiblast is essential for its correct patterning and proper communication with the extraembryonic lineages. Altogether, these results not only dissect molecular details of de novo apical-basal polarity formation, but also have broader implications for epithelial polarity and development.
2022-06-14 | PXD028315 | 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: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.
2012-02-29 | GSE35165 | GEO
Project description:Vangl is a planar cell polarity (PCP) core protein essential for aligned cell orientation along the epithelial plane perpendicular to the apical-basal direction, which is important for tissue morphogenesis, development and collective cell behavior.
2024-07-25 | PXD054233 |
Project description:CDC42 controlled apical-basal polarity regulates intestinal stem cell to transit amplifying cell fate transition via YAP-EGF-mTOR signaling
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Project description:The evolution of the human cerebral cortex involved modifications in the composition and proliferative potential of the neural stem cell (NSC) niche during brain development. Genetic changes that altered the activity of transcriptional enhancers have been linked to phenotypic differences between humans and other primates. Human Accelerated Regions (HARs) consist of >1600 highly constrained noncoding regions of the genome that show significant evolutionary acceleration on the human lineage, suggesting they encode human-specific functions. Multiple studies support that HARs include neurodevelopmental enhancers with novel activities in humans, but the regulatory roles of HARs in NSC biology has not been empirically assessed at scale. Here we conducted a direct-capture Perturb-seq screen repressing 180 neurodevelopmentally active HARs in human iPSC-derived NSCs with single-cell transcriptional readout. After profiling over 188,000 NSCs, we identified a set of HAR perturbations with convergent transcriptional effects on gene networks related to the specification of basal radial glia (bRG), a progenitor population that is expanded in humans. Processes associated with these networks included the regulation of apicobasal polarity and migration. We found convergent dysregulation of specific apicobasal polarity and adherens junction regulators, including PARD3, ABI2, SETD2, and PCM1, which are critical to apical-basal RG fate decisions. Autism- and intellectual-disability-associated genes were also enriched among genes showing changes in expression due to HAR perturbations. Our findings reveal interconnected roles for HARs in NSC biology and cortical development and link specific HARs to processes implicated in human cortical expansion.
2024-07-05 | GSE270828 | GEO
Project description:Epithelial polarity is controlled by a polarity machinery including the Rho GTPase CDC42 and Scribble/PAR. By using intestinal stem cell (ISC)-specific deletion of CDC42 in Olfm4-IRES-eGFPCreERT2;CDC42flox/flox mice, we found that ISC-initiated CDC42 loss caused a drastic hyper-proliferation of transit amplifying (TA) cells and disrupted epithelial polarity. CDC42-null crypts displayed expanded TA cell and diminished ISC populations, accompanied by elevated hippo signaling via YAP/TAZ - Ereg and mTOR activation, independent from canonical Wnt signaling. YAP/TAZ conditional knockout restored the balance of ISC/TA cell populations and crypt proliferation but did not rescue the polarity in CDC42-null small intestine. mTOR or EGFR inhibitor treatment of CDC42 KO mice exhibited similar rescuing effects without affecting YAP/TAZ signaling. Inducible ablation of Scribble in intestinal epithelial cells mimics that of CDC42 KO defects including crypt hyperplasia and hippo signaling activation. Mammalian epithelial polarity regulates ISC and TA cell fate and proliferation via a hippo-Ereg-mTOR cascade.
2021-10-23 | GSE166736 | GEO
Project description:Identification of genes regulated by apical auxin and basal cytokinin treatment of the nodal stem in cauline buds of Arabidopsis thaliana
2016-12-25 | GSE59741 | GEO
Project description:After section, Hydra regenerate each missing part within 2 to 3 days. This study was designed to allow tracking of gene expression levels during apical and basal regeneration and to compare these different regenerative contexts systematically. We determine that transient early genetic events are generic, i.e. that modulations in gene expression have analogous directions, magnitudes and durations whatever the level along the central body column and orientation of the amputation plane. In turn, early modulated transcripts with sustained expression patterns during regeneration are generally distinct during apical and basal regeneration. Genes that were previously shown to be instrumental in defining the apical organizer (Wnt signalling pathway) are among the first genes to be expressed in the condition where Hydra regenerates its apical part, Wnt3 is actually the only detected transcript encoding a signalling protein already upregulated by 2h. Regarding basal regeneration, we identify a number of transcripts with sustained expression patterns already established by 4h, some of them encoding evolutionary conserved signalling proteins, which are almost exclusively consisting of agonists and antagonists of the BMP signalling pathway. The processed data deposited here are also accessible in a graphical manner from a blast-based web interface available at https://hydratlas.unige.ch
2019-03-01 | GSE111531 | GEO