GLIS3 Transcriptionally Activates WNT Genes to Promote Differentiation of Human Embryonic Stem Cells to Posterior Neural Progenitors
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA431403 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Anterior-posterior (A-P) specification of the neural tube involves initial acquisition of anterior fate followed by the induction of posterior characteristics in the primitive anterior neuroectoderm. Several morphogens have been implicated in the regulation of A-P neural patterning; however, our understanding of factors regulating these morphogens remains incomplete. Here we show that the Krüppel-like zinc finger transcription factor GLI-Similar 3 (GLIS3) directs differentiation of human embryonic stem cells into posterior neural progenitor cells in lieu of the default anterior pathway. Transcriptomic analyses reveal that this switch in cell fate is due to rapid activation of an autocrine WNT signaling pathway. Mechanistically, through genome-wide RNA-Seq, ChIP-Seq and functional analyses, we show that GLIS3 binds to and directly regulates the transcription of several WNT genes, including the strong posteriorizing factor WNT3A. Inhibition of WNT signaling is sufficient to abrogate GLIS3-induced posterior specification. Altogether, our findings suggest a critical role for GLIS3 in A-P specification through the direct transcriptional activation of WNT genes.
2018-11-21 | GSE109562 | GEO
Project description: Not available
| S-EPMC6368876 | biostudies-literature
Project description:Decrease in Cdx dosage in an allelic series of mouse Cdx mutants leads to progressively more severe posterior vertebral defects. These defects are corrected by posterior gain of function of the Wnt effector Lef1. Precocious expression of Hox paralogous 13 genes also induces vertebral axis truncation by antagonizing Cdx function. We report here that the phenotypic similarity also applies to patterning of the caudal neural tube and uro-rectal tracts in Cdx and Wnt3a mutants, and in embryos precociously expressing Hox13 genes. Cdx2 inactivation after placentation leads to posterior defects including incomplete uro-rectal septation. Compound mutants carrying one active Cdx2 allele in the Cdx4 null background (Cdx2/4), transgenic embryos precociously expressing Hox13 genes, and a novel Wnt3a hypomorph mutant all manifest a comparable phenotype with similar urorectal defects. Phenotype and transcriptome analysis in early Cdx mutants, genetic rescue experiments and gene expression studies lead us to propose that Cdx transcription factors act via Wnt signalling during the laying down of urorectal mesoderm, and that they are operative in an early phase of these events, at the site of tissue progenitors in the posterior growth zone of the embryo. Cdx and Wnt mutations and premature Hox13 expression also cause similar neural dysmorphology including ectopic neural structures sometimes leading to neural tube splitting at caudal axial levels. These findings involve the Cdx genes, canonical Wnt signalling, and the temporal control of posterior Hox gene expression in posterior morphogenesis in the different embryonic germ layers. They shed a new light on the etiology of the Caudal Dysplasia or Caudal Regression range of human congenital defects. We used dissected Cdx2 null mutant versus wild type embryos at the 4/5 somite and 7/8 somite stage. RNA was isolated from the posterior part of the embryos (20 embryos of each genotype and stage), dissected at the same axial levels by using the last somite boundary and the base of the allantois as landmarks. Differentially labelled cRNA from the Cdx2 and control embryos were hybridized on 4X44K Agilent Whole Mouse Genome dual colour Microarrays (G4122F) in two dye swap experiments and two technical replicates, resulting in eight individual arrays.
2011-12-01 | E-GEOD-30113 | biostudies-arrayexpress
Project description:Decrease in Cdx dosage in an allelic series of mouse Cdx mutants leads to progressively more severe posterior vertebral defects. These defects are corrected by posterior gain of function of the Wnt effector Lef1. Precocious expression of Hox paralogous 13 genes also induces vertebral axis truncation by antagonizing Cdx function. We report here that the phenotypic similarity also applies to patterning of the caudal neural tube and uro-rectal tracts in Cdx and Wnt3a mutants, and in embryos precociously expressing Hox13 genes. Cdx2 inactivation after placentation leads to posterior defects including incomplete uro-rectal septation. Compound mutants carrying one active Cdx2 allele in the Cdx4 null background (Cdx2/4), transgenic embryos precociously expressing Hox13 genes, and a novel Wnt3a hypomorph mutant all manifest a comparable phenotype with similar urorectal defects. Phenotype and transcriptome analysis in early Cdx mutants, genetic rescue experiments and gene expression studies lead us to propose that Cdx transcription factors act via Wnt signalling during the laying down of urorectal mesoderm, and that they are operative in an early phase of these events, at the site of tissue progenitors in the posterior growth zone of the embryo. Cdx and Wnt mutations and premature Hox13 expression also cause similar neural dysmorphology including ectopic neural structures sometimes leading to neural tube splitting at caudal axial levels. These findings involve the Cdx genes, canonical Wnt signalling, and the temporal control of posterior Hox gene expression in posterior morphogenesis in the different embryonic germ layers. They shed a new light on the etiology of the Caudal Dysplasia or Caudal Regression range of human congenital defects.
2011-12-01 | GSE30113 | GEO
Project description:Purpose: Combination of systemic RNAi with RNAseq to identify target genes of important pathways in early development Wnt/β-catenin and hedgehog (Hh) signaling are essential for transmitting signals across cell membranes in animal embryos. Early patterning of the principal insect model, Drosophila melanogaster, occurs in the syncytial blastoderm, where diffusion of transcription factors obviates the need for signaling pathways. However, in the cellularized growth zone of typical short germ insect embryos, signaling pathways are predicted to play a more fundamental role. Indeed, the Wnt/β-catenin pathway is required for posterior elongation in most arthropods, although which target genes are activated in this context remains elusive. Here, we use the short germ beetle Tribolium castaneum to investigate two Wnt and Hh signaling centers located in the head anlagen and in the growth zone of early embryos. We find that Wnt/β-catenin signaling acts upstream of Hh in the growth zone, whereas the opposite interaction occurs in the head. We determine the target gene sets of the Wnt/β-catenin and Hh pathways and find that the growth zone signaling center activates a much greater number of genes and that the Wnt and Hh target gene sets are essentially non-overlapping. The Wnt pathway activates key genes of all three germ layers, including pair-rule genes, and Tc-caudal and Tc-twist. Furthermore, the Wnt pathway is required for hindgut development and we identify Tc-senseless as a novel hindgut patterning gene required in the early growth zone. At the same time, Wnt acts on growth zone metabolism and cell division, thereby integrating growth with patterning. Posterior Hh signaling activates several genes potentially involved in a proteinase cascade of unknown function.
2014-02-06 | GSE54706 | GEO
Project description:Adult pancreatic progenitor cells are a potential source of renewable insulin producing cells that can be used in regenerative medicine and cell replacement therapy for type-1 diabetes. We sought to understand the mechanisms by which adult pancreatic progenitor cells undergo self-renewal. The effects of knockdown of Glis3, CD133 (Prominin-1) and beta-catenin were investigated and we found that Glis3 and CD133 are capable of regulating self-renewal through Wnt gene expression.
2019-06-30 | GSE124944 | GEO
Project description:Purpose: Combination of systemic RNAi with RNAseq to identify target genes of important pathways in early development Drosophila early patterning occurs in the syncytial blastoderm where transcription factors diffuse between cells. However, in typical insect embryos, patterning occurs in a cellularized environment where signaling pathways are likely to play a more fundamental role. We use the short germ beetle Tribolium castaneum to investigate two putative Wnt and Hh signaling centers located in the anlagen of head and growth zone. These structures are known to develop in a different way in short germ insects. We find that Hh acts upstream of Wnt in the head, which is different from the Drosophila situation. In the growth zone Wnt signaling acts upstream. For the first time outside Drosophila, we comprehensively determine the Wnt and Hh target gene sets and distinguish the anterior from the posterior gene sets by genetically depleting head or growth zone. Surprisingly, there are significantly more targets in the growth zone than in the head for both pathways and we find that their growth zone gene sets are essentially non-overlapping. Furthermore, several pair rule genes, Tc-caudal, Tc-twist and hindgut patterning genes are regulated by Wnt signaling. In addition, Wnt controls growth zone metabolism and cell division. Posterior Hh signaling activates several genes potentially involved in a proteinase cascade of unknown function. Unexpectedly, we find the Wnt target Tc-senseless to be required for hindgut development. 10-11 h old whole embyro mRNA profiles of the following treatments: reference: wild type 100bp single read triplicates reference: wild type 50bp single read triplicates treatment: Tc-arrow RNAi knockdown 50 bp single read triplicates treatment: Tc-frizzled1/2 RNAi double knockdown 50 bp single read triplicates treatment: Tc-hedgehog RNAi knockdown 100bp single reads quadruplicates treatment: Tc-orthodenticle RNAi knockdown 100bp single reads triplicates treatment: Tc-torso RNAi knockdown 100bp single reads triplicates treatment: Tc-wntless RNAi knockdown 50bp single reads triplicates Total: 2 references, 6 treatments, 25 sequencing runs
2014-02-06 | E-GEOD-54706 | biostudies-arrayexpress
Project description:The hippocampus plays major roles in learning and memory. Similar to other parts of the brain, the development of hippocampus requires precise coordination of patterning, cell proliferation, differentiation, and migration, with both cell-intrinsic and extrinsic mechanisms involved. Here we genetically removed the chromatin-association capability of KDM2B - a key component of the variant Polycomb repressive complex 1 (PRC1) - in the developing dorsal telencephalon (Kdm2bEmx1-∆CxxC) to surprisingly discover that the size of Kdm2bEmx1-∆CxxC hippocampus, particularly the dentate gyrus, became drastically smaller with disorganized cellular components and structure. Kdm2bEmx1-∆CxxC mice displayed prominent defects in spatial memory, motor learning and fear conditioning. The differentiation path of the developing Kdm2bEmx1-∆CxxC hippocampus was greatly delayed, with significant amount of TBR2-expressing intermediate progenitors being stuck along the migratory path. Transcriptome and chromatin immunoprecipitation studies of neonatal hippocampi and their progenitors indicated that genes implicated in stemness maintenance, especially components of canonical Wnt signaling, could not be properly silenced by PRC1 and PRC2. Activating Wnt signaling disturbed hippocampal neurogenesis, recapitulating the effect of KDM2B loss. Together, we unveiled a previously unappreciated gene repressive program mediated by KDM2B that controls progressive fate specifications and cell migration, hence morphogenesis of hippocampus during development.
2023-09-25 | GSE222463 | GEO
Project description:The hippocampus plays major roles in learning and memory. Similar to other parts of the brain, the development of hippocampus requires precise coordination of patterning, cell proliferation, differentiation, and migration, with both cell-intrinsic and extrinsic mechanisms involved. Here we genetically removed the chromatin-association capability of KDM2B - a key component of the variant Polycomb repressive complex 1 (PRC1) - in the developing dorsal telencephalon (Kdm2bEmx1-∆CxxC) to surprisingly discover that the size of Kdm2bEmx1-∆CxxC hippocampus, particularly the dentate gyrus, became drastically smaller with disorganized cellular components and structure. Kdm2bEmx1-∆CxxC mice displayed prominent defects in spatial memory, motor learning and fear conditioning. The differentiation path of the developing Kdm2bEmx1-∆CxxC hippocampus was greatly delayed, with significant amount of TBR2-expressing intermediate progenitors being stuck along the migratory path. Transcriptome and chromatin immunoprecipitation studies of neonatal hippocampi and their progenitors indicated that genes implicated in stemness maintenance, especially components of canonical Wnt signaling, could not be properly silenced by PRC1 and PRC2. Activating Wnt signaling disturbed hippocampal neurogenesis, recapitulating the effect of KDM2B loss. Together, we unveiled a previously unappreciated gene repressive program mediated by KDM2B that controls progressive fate specifications and cell migration, hence morphogenesis of hippocampus during development.
2023-09-25 | GSE222462 | GEO
Project description:The hippocampus plays major roles in learning and memory. Similar to other parts of the brain, the development of hippocampus requires precise coordination of patterning, cell proliferation, differentiation, and migration, with both cell-intrinsic and extrinsic mechanisms involved. Here we genetically removed the chromatin-association capability of KDM2B - a key component of the variant Polycomb repressive complex 1 (PRC1) - in the developing dorsal telencephalon (Kdm2bEmx1-∆CxxC) to surprisingly discover that the size of Kdm2bEmx1-∆CxxC hippocampus, particularly the dentate gyrus, became drastically smaller with disorganized cellular components and structure. Kdm2bEmx1-∆CxxC mice displayed prominent defects in spatial memory, motor learning and fear conditioning. The differentiation path of the developing Kdm2bEmx1-∆CxxC hippocampus was greatly delayed, with significant amount of TBR2-expressing intermediate progenitors being stuck along the migratory path. Transcriptome and chromatin immunoprecipitation studies of neonatal hippocampi and their progenitors indicated that genes implicated in stemness maintenance, especially components of canonical Wnt signaling, could not be properly silenced by PRC1 and PRC2. Activating Wnt signaling disturbed hippocampal neurogenesis, recapitulating the effect of KDM2B loss. Together, we unveiled a previously unappreciated gene repressive program mediated by KDM2B that controls progressive fate specifications and cell migration, hence morphogenesis of hippocampus during development.
2023-09-25 | GSE222464 | GEO