Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SIX2 and SIX3 coordinately regulate functional maturity and fate of human pancreatic β cells [RNA-seq]

ABSTRACT: Transcriptomic profiling by high-throughput sequencing of primary human Beta cells following SIX2 or SIX3 loss of function.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164626 | GEO | 2021/01/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

SIX2 and SIX3 coordinately regulate functional maturity and fate of human pancreatic β cells

Project description:Transcriptomic profiling by high-throughput sequencing of primary human Beta cells following SIX2 or SIX3 loss of function. SIX2 genome-binding profiling by CUT&RUN and high-throughput sequencing. This SuperSeries is composed of the SubSeries listed below.

2021-01-26 | GSE164628 | GEO

SIX2 and SIX3 coordinately regulate functional maturity and fate of human pancreatic β cells.

Project description:The physiological functions of many vital tissues and organs continue to mature after birth, but the genetic mechanisms governing this postnatal maturation remain an unsolved mystery. Human pancreatic β cells produce and secrete insulin in response to physiological cues like glucose, and these hallmark functions improve in the years after birth. This coincides with expression of the transcription factors SIX2 and SIX3, whose functions in native human β cells remain unknown. Here, we show that shRNA-mediated SIX2 or SIX3 suppression in human pancreatic adult islets impairs insulin secretion. However, transcriptome studies revealed that SIX2 and SIX3 regulate distinct targets. Loss of SIX2 markedly impaired expression of genes governing β-cell insulin processing and output, glucose sensing, and electrophysiology, while SIX3 loss led to inappropriate expression of genes normally expressed in fetal β cells, adult α cells, and other non-β cells. Chromatin accessibility studies identified genes directly regulated by SIX2. Moreover, β cells from diabetic humans with impaired insulin secretion also had reduced SIX2 transcript levels. Revealing how SIX2 and SIX3 govern functional maturation and maintain developmental fate in native human β cells should advance β-cell replacement and other therapeutic strategies for diabetes.

| S-EPMC7849364 | biostudies-literature

SIX2 and SIX3 coordinately regulate functional maturity and fate of human pancreatic β cells

Project description:SIX2 and SIX3 coordinately regulate functional maturity and fate of human pancreatic β cells

| PRJNA691362 | ENA

SIX2 and SIX3 coordinately regulate functional maturity and fate of human pancreatic β cells [RNA-seq]

Project description:SIX2 and SIX3 coordinately regulate functional maturity and fate of human pancreatic β cells [RNA-seq]

| PRJNA691365 | ENA

Exploring Six2 distal enhancer interactome in developing mouse kidney

Project description:The Six2 distal enhancer regulates expression of the 60 kb-downstream gene Six2, but does not regulate the Six3 gene which is 70 kb further downstream. CTCF ChIP-Seq and Hi-C data points to a chromatin domain boundary between Six2 and Six3 which may intervene interaction between Six2-DE and Six3. The irradiation-induced Brachyrrhine (Br) mutant allele was found to carry a 320 kb genomic inversion that includes Six2 and Six3, but not Six2DE. This repositioned Six2 under Six3 enhancer control and Six3 under Six2 distal enhancer control. Consistent with this, Six3 is ectopically expressed in Br/+ kidneys and Six2 expression is reduced. To test whether there is a change of interaction between Six2 distal enhancer and Six2 or Six3 promoters, we performed 4C-Seq in E16.5 wildtyp or Br/+ mice nephron-genic zone cells.

2018-01-18 | GSE108102 | GEO

Sp8 and Sp9 coordinately promote D2-type medium spiny neuron production by activating Six3 expression [ChIP-Seq]

Project description:D1- and D2-type medium spiny neurons (MSNs) are the principal projection neurons in the striatum, including in the dorsal striatum (caudate nucleus and putamen) and ventral striatum (nucleus accumbens and olfactory tubercle) that are generated by the lateral ganglionic eminence (LGE). Using conditional deletion, we show that mice lacking the Sp8 and Sp9 transcription factors (TFs) selectively have a severe reduction in D2 MSNs due to reduced neurogenesis in the LGE. Sp8/9 together drive expression of the Six3 TF in a spatial restricted domain of the LGE subventricular zone. Conditional deletion of Six3 also prevents the formation of most D2 MSNs, phenocopying the Sp8/9 loss of function. Finally, ChIP-Seq reveals that SP9 directly binds to the promoter and a putative enhancer of Six3. This study provides evidence for components of a transcription pathway, in a regionally restricted LGE domain, that selectively drives the generation of D2 MSNs.

2018-05-11 | GSE114306 | GEO

Finding genomic targets of transcription factor Six3 in neural stem cells.

Project description:Pro-neural transcription factor Six3 has been implicated in neuronal differentiation. We established primary neural stem cell with Six3 overexpression, and utilized CUT&RUN to profile genomic loci bound by Six3.

2022-07-17 | GSE208169 | GEO

Gene expression profiling of Six2-positive nephron progenitors from mouse embryo

Project description:Nephron progenitors in the embryonic kidney propagate while generating differentiated nephrons. However, the progenitors in mice terminally differentiate shortly after birth. We defined culture conditions to selectively propagated nephron progenitors in vitro in an undifferentiated state. To understand how expression profiles of Six2+ cells changed during culture in vitro compared with in vivo, we performed microarray analysis of Six2+ cells at E11.5 (starting material) and P0 (experiencing 8 days in vivo), and cultured Six2+ cells at E11.5 for 8 days or 19 days. Microarray analysis were performed with isolated Six2-positive nephron progenitors from transgenic mice embryo at E11.5 or P0, and cultured E11.5 Six2+ cells for 8 or 19 days in conditioned media. P0 non-progenitors represent Six2-GFP-negative cells at P0.

2016-04-14 | E-GEOD-79024 | biostudies-arrayexpress

Genome-wide maps of Six2 and b-catenin in mesenchymal nephron progenitors

Project description:Self-renewing undifferentiated nephron progenitors express Six2, a transcription factor that is required for their maintenance as undifferentiated progenitors. Differentiation of nephron progenitors is triggered by Wnt/b-catenin signaling. In order to understand how Six2 and Wnt signaling counteract each other, we performed ChIP-seq of Six2 and b-catenin in mesenchymal nephron progenitor cells. Nephron progenitors were FACS-isolated from BAC transgenic Six2GFPcre-positive embryonic kidneys at E16.5. For Six2 ChIP, freshly FACS isolated Six2+ cells were used. For b-catenin ChIP, FACS isolated Six2+ cells were aggregated by centrifugation at 850g for 5min and incubated in 10%FBS/DMEM containing 4uM BIO for 24hrs.

2012-09-11 | E-GEOD-39837 | biostudies-arrayexpress

Epigenomic landscapes of human primary pancreatic cell types

Project description:Intensive efforts are focused on identifying regulators of human pancreatic islet cell growth and maturation to accelerate development of therapies for diabetes. After birth, islet cell growth and function are dynamically regulated; however, establishing these age-dependent changes in humans has been challenging. Here we describe a multimodal strategy for isolating pancreatic endocrine and exocrine cells from children and adults to identify age-dependent gene expression and chromatin changes on a genomic scale. These profiles revealed distinct proliferative and functional states of islet alpha-cells or beta-cells, and histone modifications underlying age-dependent gene expression changes. Expression of SIX2 and SIX3, transcription factors without prior known functions in the pancreas and linked to fasting hyperglycemia risk, increased with age specifically in human islet beta-cells. SIX2 and SIX3 were sufficient to enhance insulin content or secretion in immature beta-cells. Our work provides a unique resource to study human-specific regulators of islet cell maturation and function.

2016-04-14 | GSE65793 | 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