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

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

PROVIDER: PRJNA691362 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13410308_1.fastq.gz	Fastqsanger.gz
	SRR13410308_2.fastq.gz	Fastqsanger.gz
	SRR13410309_1.fastq.gz	Fastqsanger.gz
	SRR13410309_2.fastq.gz	Fastqsanger.gz
	SRR13410310_1.fastq.gz	Fastqsanger.gz

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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 [RNA-seq]

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

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

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

2021-01-26 | GSE164626 | 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

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 Striatal Medium Spiny Neuron Production through Activating Six3 Expression

Project description:Sp8 and Sp9 Coordinately Promote Striatal Medium Spiny Neuron Production through Activating Six3 Expression

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SWI/SNF chromatin remodelers target enhancers via interaction with Eya1 and Six2 to specify metanephric fate and maintain nephron progenitor pool

Project description:Eya1 is a critical regulator for establishing nephron fate and acts upstream of Six2. However, how Eya1-centered network operates remains elusive. Here we identified Eya1's interacting factors via mass-spectrometry and show that Eya1 and Six2 interact with Brg1-based SWI/SNF chromatin-remodeling complex in the kidney. Brg1 specifies the nephron fate and regulates Eya1 expression through binding to multiple cis-regulatory-elements. In the nephron-progenitors, Brg1/Six2 co-occupy cis-regulatory-elements at key loci and Brg1-recruitment to many of these regions is disrupted in the absence of Six2. We demonstrate Six2-dependent Brg1-occupancy to Mycn promoter and two distal enhancers of Pbx1, all of which direct nephron-progenitor-specific expression in response to binding to Six2. RNA-seq analysis reveals that depletion of Brg1 leads to upregulation of genes for podocyte-lineages and aberrant activation of cell-death inducing factors. Together, this study highlights an essential function of the Brg1-BAFs in cooperation with Eya1/Six2 in enhancer-mediated regulation of gene expression in the nephron-progenitors.

2023-10-12 | GSE159483 | 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

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

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

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