Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

NGN3 oscillatory expression controls the timing of human pancreatic endocrine differentiation

ABSTRACT: Understanding protein expression dynamics is crucial for the mechanistic understanding of cell differentiation. We investigate the dynamics and decoding of NGN3, a transcription factor critical for pancreatic endocrine development. A knock-in endogenous reporter shows that NGN3 protein oscillates with a 13-hour periodicity in human iPS-derived endocrine progenitors and is switched off as cells differentiate to β-like and pre-alpha cells. Increasing NGN3 protein stability results in one broad peak of expression instead of oscillations, with a larger peak to trough fold-change. This leads to precocious endocrine differentiation and earlier expression of key NGN3 target genes. Single-cell analysis of dynamics, mathematical modelling and experimental validation suggest that NGN3 oscillations are decoded by fold-change detection (FCD) rather than the level of expression via an incoherent feedforward loop motif (IFFL) that explains both normal and precocious differentiation. Our findings suggest that oscillatory NGN3 dynamics control the timing of differentiation, but not fate specification.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281587 | GEO | 2025/03/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identifying new interactors of NGN3 through IP-MS

Project description:NGN3 is a transcription factor whose transient expression during pancreatic development is vital for the generation of endocrine pancreatic cells, including beta cells. NGN3 stabilisation has been shown to induce exocrine-to-endocrine cell plasticity in the murine pancreas, making it a viable target for therapies aiming to replenish beta cells after immune-mediated destruction in type 1 diabetes patients. Here, we set out to identify new interactors of NGN3 that could play a role in its post-translational regulation. We transfected HEK293A cells with HA-tagged NGN3 and carried out immunoprecipitation of the HA-tag, followed by analysis of co-immunoprecipitated interactors via LC-MS/MS.

2023-03-27 | PXD033691 | Pride

Expression data from Xenopus endoderm at stage 15 following four hours of Ngn3-GR overexpression

Project description:Ngn3 is a master regulator of pancreatic endocrine development. It is necessary for the creation of all endocrine cells in mice. Little is known about the genes that act downstream of the transcription factor Ngn3 in pancreas endocrine development to specify each of the endocrine lineages. As a consequence, little is known about the genes involved in early development and the specification of the beta cell. We used microarrays to identify Ngn3 downstream genes that are involved in early and ectopic beta cell development in Xenopus laevis. We overexpressed Ngn3 in the Xenopus early endoderm and analyzed the genes that are upregulated four hours after.

2012-04-01 | GSE29017 | GEO

Transcriptional profiling of Ngn3-dependent pancreatic endocrine differentiation at E15.5

Project description:This experiment used RNA-Seq technology to explore gene expression in mouse Ngn3^GFP/+ [het] FACS sorted pancreatic cells at E15.5 (commited endocrine progenitor cells) and in Ngn3^GFP/GFP [null] at E15.5 (defective endocrine progenitor cells). This experiment is designed to understand the gene expression alteration in the endocrine lineage at different embryonic days. The aim is to understand both Ngn3 dependent and independent gene expression profiles so as to reveal the instructive signals that specfy the collective endocrine islet cell fate or specific islet cell type.

2015-10-01 | E-MTAB-3352 | biostudies-arrayexpress

Transcription profiling of mouse Ngn3 expressing cells and endocrine pancreatic cells from wild type and Ngn3 mutant animals at day 15 of embryonic development

Project description:The basic helix-loop-helix transcription factor Neurogenin3 (Ngn3/Neurog3) is expressed in endocrine progenitor cells in the embryonic mouse pancreas. Ngn3 controls endocrine cell fate decisions. Ngn3 deficient mice do not develop any pancreatic endocrine cells, including insulin producing beta cells, and die postnatally from diabetes. Therefore, the characterization of gene expression in Ngn3-expressing cells and their progeny is of particular interest for the development of novel strategies for cell replacement therapies in type-1 diabetes. Here we describe two studies. In the first study (8 assays) we used mice where the EYFP (Enhanced Yellow fluorescent Protein) is expressed under the control of Ngn3 regulatory elements (knock add on strategy). EYFP-positive, Ngn3-expressing cells, were FACS sorted from embryonic pancreas at day 15.5 (E15.5), as well as EYFP-negative cells. In the second study (6 assays) we compared wild-type and Ngn3 mutant pancreas at E15.5. All samples were hybridized to Affymetrix GeneChip Mouse Genome 430.2.0 array.

2009-12-03 | E-CBIL-48 | biostudies-arrayexpress

The expression order determines the pioneer functions of Ngn3 and NeuroD1 in pancreatic endocrine differentiation

Project description:This study investigates the roles of Ngn3 and NeuroD1 in pancreatic endocrine differentiation. Using a new mouse model, we mapped NGN3 binding sites by CUT&RUN and demonstrated its pioneering role in making chromatin accessible by scATAC-seq. According to conditional knock-out and over-expression experiments and scRNA-seq, we domonstrated that NGN3's pioneering function was dose tolerance, with low doses sufficing, while NeuroD1, as a conventional TF, has no significant pioneer effects under normal phenomena. But when NGN3 was absent, NeuroD1 can alternatively acted as a pioneer factor, and sequential expression of NeuroD1 ahead of Ngn3 predominantly drives α-cell generation.

2025-02-15 | GSE270915 | GEO

The expression order determines the pioneer functions of Ngn3 and NeuroD1 in pancreatic endocrine differentiation -2

2025-02-15 | GSE271546 | GEO

Inducible Ngn3 Embryonic Stem Cells

Project description:Expression of the proendocrine gene neurogenin 3 (Ngn3) is required for the development of pancreatic islets. In order to better characterize the molecular events regulated by Ngn3 during development, we have determined the expression profile of differentiating murine embryonic stem cells (mESCs) uniformly induced to overexpress Ngn3. An ESC line was created that allows for the induction of Ngn3 by adding doxycycline (Dox) to the culture medium. Genome-wide microarray analysis was performed to identify genes regulated by Ngn3 in a variety of both undifferentiated and differentiated conditions. Characterization of pancreatic developmental markers during embryoid body (EB) formation revealed an optimum context for Ngn3 induction. Neuroendocrine genes including neurogenic differentiation 1 (NeuroD1) and single minded 1 (Sim1) were found to be significantly upregulated. Genes regulated by Ngn3 independent of the context were analyzed using systematic gene ontology tools and revealed Notch signaling as the most significantly regulated signaling pathway (p=0.009). This result is consistent with the hypothesis that Ngn3 expression makes the cell competent for Notch signaling to be activated and conversely, more sensitive to Notch signaling inhibition. Indeed, EBs induced to express Ngn3 were significantly more sensitive to gamma-secretase inhibitor-mediated Notch signaling inhibition (p<0.0001). Moreover, we find that Ngn3 induction in differentiating ESCs results in significant increases in insulin, glucagon, and somatostatin transcription. Keywords: Ngn3 induction, embryonic stem cell differentiation

2006-07-01 | GSE3653 | GEO

RNA-sequencing analysis of NGN3-GFP positive and negative cells purified from differentiating human embryonic stem cells

Project description:NGN3-eGFP could be used to mark endocrine progenitor cells and their progeny in differentiating hESCs, suggesting that profiling analysis of NGN3-eGFP+ cells could lead to the discovery of novel gene participation. Six batches of NGN3-eGFP+ and NGN3-eGFP -cells purified by FACS from a reporter hES cell line cell cultures at stage 4 were pooled together, respectively. RNA-seq-based analysis of the two cell fractions identified a total of 3976 differentially expressed genes (P-value<0.05; Fold >2), of which 72% are enriched in NGN3-GFP+ cells. As expected, all the genes expressed in pancreatic progenitor cells are enriched in NGN3-eGFP-cells; while all endocrine-associated genes are enriched in NGN3-eGFP+ cells. Among the 3976 genes, 195 have potential transcriptional factor activity and 453 are potential non-coding RNA genes, most of which have not been well investigated in pancreatic endocrine cells. The gene ontology term ‘integral to membrane’ GO: 0016021 identified 1003 differentially expressed genes that encoded ion channels, adhesion molecules and transporters.

2014-09-12 | GSE54879 | GEO

Transcriptional profiling of Ngn3-dependent pancreatic endocrine differentiation at E15.5

Project description:Transcriptional profiling of Ngn3-dependent pancreatic endocrine differentiation at E15.5

| PRJEB8694 | ENA

Induced overexpression of Pdx1 and Ngn3 in a mouse ES cell-derived endoderm population induces pancreatic differentiation

Project description:Induced overexpression of Pdx1 in activin-induced endoderm population resulted in the upregulation of pancreas-related genes such as insulin 1 and 2 at day 20. To enhance the developmental progression from the pancreatic bud to the formation of the endocrine lineages, we next expressed neurogenin3 (Ngn3) together with Pdx-1. Induced overexpression of Pdx1 together with Ngn3 dramatically increased Insulin 1 mRNA by day 9 differentiation. The levels of insulin 1 mRNA present in the induced EBs represented approximately 100 % of that found in insulinoma cell line, betaTC6. We also confirmed insulin and C-peptide staining by immunohistochemistry. These cells process and secrete insulin and respond to various insulin secretagogues. These inductive effects were restricted to c-kit+ endoderm enriched EB-derived populations suggesting that Pdx1/Ngn3 functions at the level of pancreatic specification of endoderm in this model. Microarray analysis showed that Pdx1/Ngn3 regulated the expression of a broad spectrum of pancreatic endocrine cell-related genes.

2010-08-24 | GSE23752 | 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