Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

GLIS3 Transcriptionally Activates WNT Genes to Promote Differentiation of Human Embryonic Stem Cells to Posterior Neural Progenitors

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE109562 | GEO | 2018/11/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

GLIS3

Project description:GLIS3

| PRJNA1002242 | ENA

Rational derivation of midbrain dopamine neuron progenitors from hPSCs using a selective FZD5 antibody agonist [scRNA-Seq]

Project description:Current ventral midbrain dopaminergic progenitor differentiation protocols utilize small molecule inhibitors targeting Glycogen synthase kinase-3 (GSK3) to activate Wnt signaling, a step required for the anterior-posterior patterning of the nervous system and acquisition of the midbrain fate. However, GSK3a and GSK3β are pleiotropic kinases involved in multiple signaling pathways and their inhibition is a known trigger of neurogenesis. We predicted that direct activation of specific Wnt receptors naturally involved during neural patterning would allow for a more precise spatiotemporal control of Wnt/β-catenin signaling and mimic endogenous cell-cell communication mechanisms to improve hPSC differentiation. Here, we characterized the expression of FZD receptors at the surface of neural progenitor cells with different regional identity. Our data shows that FZD5 expression is uniquely upregulated in anterior neural progenitors and is rapidly downregulated as cells adopt a posterior fate. This spatial regulation of Frizzled cell surface expression constitutes a novel regulatory mechanism adjusting the levels of β-catenin signaling along the anterior-posterior axis and possibly contribute to midbrain-hindbrain boundary formation. Using a tetravalent antibody that selectively triggers FZD5 and LRP6 clustering to activate Wnt/β-catenin signaling, we show that the resulting midbrain-patterned neural progenitors exhibit a gene expression program more closely aligned with the anatomical origin of dopaminergic neurons and could hence represent a more efficient source for cell transplant therapies.

2024-02-21 | GSE241042 | GEO

Rational derivation of midbrain dopamine neuron progenitors from hPSCs using a selective FZD5 antibody agonist [RNA-Seq]

2024-02-21 | GSE241041 | GEO

GLIS3 Transcriptionally Activates WNT Genes to Promote Differentiation of Human Embryonic Stem Cells to Posterior Neural Progenitors

Project description:GLIS3 Transcriptionally Activates WNT Genes to Promote Differentiation of Human Embryonic Stem Cells to Posterior Neural Progenitors

| PRJNA431403 | ENA

Brief suppression of SUMOylation in embryonic stem cells generates embryo-like structures

Project description:Recent advances in synthetic mammalian embryo models have opened new avenues to understand the complex events controlling lineage specification and morphogenetic processes occurring during peri-implantation and early organogenesis. Two main strategies have been developed to build embryo-like structures (ELSs): by assembling extraembryonic and embryonic stem cells (ESCs) or by subjecting ESCs to various morphogens. Here, we show that mouse ESCs solely exposed to chemical inhibition of SUMOylation, a post-translational modification which acts as a general chromatin barrier to cell fate transitions, generates ELSs comprising both anterior neural and trunk-associated regions. HypoSUMOylation-instructed ESCs first give rise to adherent spheroids which, once in suspension, self-organize into gastrulating structures containing cell types spatially and functionally related to embryonic and extraembryonic compartments. Alternatively, spheroids cultured in an optimized droplet-microfluidic device form elongated structures that undergo axial organization reminiscent of natural embryo morphogenesis. Single-cell RNA-sequencing further revealed a variety of cellular lineages including properly positioned anterior neuronal cell types, Schwann cell precursors and paraxial mesoderm segmented into somite-like structures. Mechanistically, transient SUMOylation suppression gradually increases DNA methylation genome-wide and repressive marks deposition at Nanog, enhancing ESC plasticity. Our approach provides a proof of principle for a potential strategy to study early embryogenesis by targeting molecular roadblocks of cell fate change to shape multicellular architecture.

2023-04-13 | PXD031548 | Pride

Construction of a Mammalian Embryo from Embryonic Stem Cells Instructed by Morphogen Gradients

Project description:Generating properly organized and differentiated embryonic structures in vitro from aggregates of pluripotent cells remains a major challenge. In a living embryo, the interplay in between signaling molecules known as morphogens and their antagonists lead to gradients of activity that instruct cells about their fate, leading to patterning and morphogenesis. Here we show that experimentally engineering a morphogen signaling center within an aggregate of mouse pluripotent stem cells is sufficient to mimic the function of an embryo organizer and to trigger embryonic development. The resulting embryoids are remarkably well patterned along anterior-posterior and dorsal-ventral axes, generate three germ layers through a process of gastrulation and differentiate germ layer derivatives (including notochord, vasculature, neural tube, neural crest, endoderm) similar to an authentic embryo at E9-E9.5.

2021-04-25 | GSE142309 | GEO

Regulation of GLIS3 in neonatal kidney development

Project description:Loss of transcription factor GLIS3 function in humans and mice leads to the development of neonatal polycystic kidney disease (PKD). To investigate how loss of GLIS3 function in kidney affects postnatal kidney development and PKD, we analyzed the gene expression profiles of kidneys from WT and Glis3-null mice at P7, P14, and P28 by RNA-Seq analysis using Glis3 global KO model Glis3-mCherry.

2024-12-18 | GSE240532 | GEO

Regulation of gene expression by GLIS3 during neonatal kidney development

2023-12-31 | GSE240071 | GEO

T.F. Glis3: a novel critical player in the regulation of pancreatic beta-cell development and insulin gene expression

Project description:Glis3 mutant mice (Glis3zf/zf) die within the first week after birth due to overt diabetes, evidenced by hyperglycemia and hypoinsulinemia. Histopathological analysis showed that Glis3zf/zf mice develop a pancreatic phenotype with a dramatic loss of beta- (insulin) and delta- (somatostatin) cells contrasting a smaller relative loss of alpha- (glucagon), PP- (pancreatic polypeptide), and epsilon- (ghrelin) cells. Glis3zf/zf mice develop ductal cysts with decreased number of primary cilia, while the acini are not significantly affected. Gene expression profiling by microarray analysis demonstrated that the expression of terminal hormonal genes and several transcription factors important in endocrine development were significantly deregulated in Glis3zf/zf mice. During pancreatic development, Glis3 mRNA expression is induced during the secondary transition, a stage of cell lineage specification and extensive patterning. Changes in pancreatic development of Glis3zf/zf mice are noted during and after this stage. The population of pancreatic progenitors appears not to be greatly affected in Glis3zf/zf mice; however, the number of neurogenin 3 (Ngn3) positive, endocrine progenitors is significantly reduced. Our study indicates that Glis3 plays a key role in cell lineage specification, particularly the development of mature pancreatic beta-cells. In addition, we identified evidence that Glis3 regulates insulin gene expression through two Glis-binding sites in its proximal promoter indicating that Glis3 is a regulator of insulin gene expression.

2010-01-01 | GSE18172 | GEO

Glis3: The role in osteoblast differentiation and adipocyte differentiation

Project description:The expression of Glis3 in C3H10T1/2 cells promotes osteoblastic differentiation as indicated by the the induction of increase in alkaline phosphatase activity, an early marker of osteoblast differentiation, and increased expression of osteopontin, a late marker of osteogenesis. Glis3 acts synergistically with bone morphogenic protein 2 (BMP-2). In contrast, expression of Glis3 inhibits the induction of adipocyte differentiation. Microarray analysis identified the fibroblast growth factor 18 (FGF18) as one of the genes induced by Glis3 in C3H10T1/2 cells directly. Keywords: Glis3, osteoblast differentiation, adipocyte differentiation, FGF18, BMP2

2007-05-22 | GSE5379 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data