Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SMNDC1 links chromatin remodeling and splicing to regulate pancreatic hormone expression

ABSTRACT: Insulin expression is restricted to the pancreatic beta cells, which are physically or functionally depleted in diabetes. Identifying targetable pathways repressing insulin in non-beta cells, particularly in the developmentally related glucagon-secreting alpha cells, is an important aim of regenerative medicine. Here, we performed an RNA interference screen in the murine alpha cell line, alphaTC1, to identify silencers of insulin expression. We discovered that knockdown of the splicing factor Smndc1 (Survival Motor Neuron Domain Containing 1) triggered a global repression of alpha cell gene-expression programs in favor of increased beta cell markers. Mechanistically, Smndc1 knockdown upregulated the key beta cell transcription factor Pdx1, by modulating the activities of the BAF and Atrx families of chromatin remodeling complexes. SMNDC1’s repressive role was conserved in human pancreatic islets, its loss triggering enhanced insulin secretion and PDX1 expression. Our study identifies Smndc1 as a key factor connecting splicing and chromatin remodeling to the control of insulin expression in human and mouse islet cells.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Alpha-tc1.6 Cell, Beta-tc3 Cell

SUBMITTER: Frédéric FONTAINE

LAB HEAD: Stefan Kubicek

PROVIDER: PXD030363 | Pride | 2022-07-01

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	Alpha_SAINT.txt	Txt
	Beta_SAINT.txt	Txt
	CC_SKu_41-M554-F01-P7858-1.msf	Msf
	CC_SKu_41-M554-F01-P7858-1.raw	Raw
	CC_SKu_41-M554-F01-P7858-2.msf	Msf

Items per page:

1 - 5 of 76

Similar Datasets

SMNDC1 links chromatin remodeling and splicing to regulate pancreatic hormone expression

Project description:Insulin expression is restricted to the pancreatic beta cells, which are physically or functionally depleted in diabetes. Identifying targetable pathways repressing insulin in non-beta cells, particularly in the developmentally related glucagon-secreting alpha cells, is an important aim of regenerative medicine. Here, we performed an RNA interference screen in the murine alpha cell line, alphaTC1, to identify silencers of insulin expression. We discovered that knockdown of the splicing factor Smndc1 (Survival Motor Neuron Domain Containing 1) triggered a global repression of alpha cell gene-expression programs in favor of increased beta cell markers. Mechanistically, Smndc1 knockdown upregulated the key beta cell transcription factor Pdx1, by modulating the activities of the BAF and Atrx families of chromatin remodeling complexes. SMNDC1’s repressive role was conserved in human pancreatic islets, its loss triggering enhanced insulin secretion and PDX1 expression. Our study identifies Smndc1 as a key factor connecting splicing and chromatin remodeling to the control of insulin expression in human and mouse islet cells.

2022-07-01 | PXD030362 | Pride

SMNDC1 links chromatin remodeling and splicing to regulate pancreatic hormone expression

2022-07-01 | PXD030361 | Pride

Epigenomic plasticity enables human pancreatic alpha to beta cell reprogramming

Project description:Insulin-secreting β cells and glucagon-secreting α cells maintain physiological blood glucose levels, and their malfunction drives diabetes development. Using ChIP sequencing and RNA sequencing analysis, we determined the epigenetic and transcriptional landscape of human pancreatic α, β, and exocrine cells. We found that, compared with exocrine and β cells, differentiated α cells exhibited many more genes bivalently marked by the activating H3K4me3 and repressing H3K27me3 histone modifications. This was particularly true for β cell signature genes involved in transcriptional regulation. Remarkably, thousands of these genes were in a monovalent state in β cells, carrying only the activating or repressing mark. Our epigenomic findings suggested that α to β cell reprogramming could be promoted by manipulating the histone methylation signature of human pancreatic islets. Indeed, we show that treatment of cultured pancreatic islets with a histone methyltransferase inhibitor leads to colocalization of both glucagon and insulin and glucagon and insulin promoter factor 1 (PDX1) in human islets and colocalization of both glucagon and insulin in mouse islets. Thus, mammalian pancreatic islet cells display cell-type–specific epigenomic plasticity, suggesting that epigenomic manipulation could provide a path to cell reprogramming and novel cell replacement-based therapies for diabetes. Pancreatic islets were collected post-mortem from 6 human donors and subjected to FACS to separate populations of alpha, beta, and exocrine cells. Depending on the availability of resulting material, sorted islet cell populations were used for H3K4me3, H3K27me3 ChIP-seq, or RNA-seq analysis. All ChIP-seq samples have a corresponding input from the same sample.

2013-08-28 | E-GEOD-50386 | biostudies-arrayexpress

Epigenomic plasticity enables human pancreatic alpha to beta cell reprogramming

2013-08-28 | GSE50386 | GEO

Nova1 is a master regulator of alternative splicing in pancreatic beta cells

Project description:Alternative splicing (AS) is a fundamental mechanism for the regulation of gene expression. It affects more than 90% of human genes but its role in the regulation of pancreatic beta cells, the producers of insulin, remains unknown. Our recently published data indicated that the M-bM-^@M-^\neuron specificM-bM-^@M-^] Nova1 splicing factor is expressed in pancreatic beta cells. We have presently coupled specific knockdown (KD) of Nova1 with RNA-sequencing to determine all splice variants and downstream pathways regulated by this protein in beta cells. Nova1 KD altered the splicing of nearly 5000 transcripts. Pathway analysis indicated that these genes are involved in exocytosis, apoptosis, insulin receptor signalling, splicing and transcription. In line with these findings, Nova1 silencing inhibited insulin secretion and induced apoptosis basally and after cytokine treatment in rodent and human beta cells. These observations identify a novel layer of regulation of beta cell function, namely AS controlled by key splicing regulators such as Nova1. 3 batch of primary rat pancreatic beta cells were examined under 2 conditions: control and with Nova1 splicing factor knock-down

2014-10-01 | E-GEOD-59633 | biostudies-arrayexpress

Transcriptional program for induced delta cell on day10

Project description:Direct lineage conversion of adult cells is a promising approach for regenerative medicine. A major challenge of lineage conversion is to generate specific subtypes of cells, closely related cells with distinct properties. The pancreatic islets contain three major hormone-secreting endocrine subtypes: insulin+ β-cells, glucagon+ α-cells, and somatostatin+ δ-cells. We previously reported that a combination of three transcription factors, Ngn3, Mafa, and Pdx1, directly reprogram pancreatic acinar cells to β-cells. We now show that acinar cells can be converted to δ-like and α-like cells by Ngn3 and Ngn3+Mafa respectively. Thus, three major islet endocrine subtypes can be derived by acinar reprogramming. Ngn3 promotes establishment of a generic endocrine state in acinar cells at the onset of reprogramming in addition to promoting δ-specification. Mafa and Pdx1 suppress δ-specification in α- and β-cell formation. These studies identify a set of defined factors whose combinatorial actions reprogram acinar cells to distinct islet endocrine subtypes in vivo. induced beta cells samples at day 10 collected for the microarray

2013-11-20 | E-GEOD-52522 | biostudies-arrayexpress

Expression data by BRD7552 treatment in PANC-1 cells

Project description:Three master regulatory transcription factors Pdx1, MafA and Ngn3 have the ability to transdifferentiate pancreatic acinar cells to insulin-producing beta cells in mice. BRD7552 was identified as a small-molecule inducer that can upregulate the expression of Pdx1 in PANC-1 cells by high-throughput qPCR screening. We used microarrays to illustrate the mechnism of BRD7552 for PDX1 and insulin induction.

2013-03-10 | GSE44946 | GEO

Long-term correction of diabetes in mice by in vivo reprogramming of pancreatic ducts

Project description:Here, we report in vivo reprogramming of pancreatic ductal cells through intra-ductal delivery of an adenoviral vector expressing the transcription factors Pdx1, Neurog3 and Mafa (adPNM). To better understand the extent of reprogramming in induced pancreatic ductal cells, comparative single cell RNA sequencing was performed on insulin+ pancreatic ductal cells and pancreatic β-cells. Compared with pancreatic β cells, we show that insulin+ pancreatic ductal cells had established a β-cell gene expression program, albeit with immature features.

2018-05-01 | GSE109113 | GEO

Expression data by BRD7552 treatment in PANC-1 cells

2013-03-10 | E-GEOD-44946 | biostudies-arrayexpress

Transcriptional program for induced delta cell on day10

2013-11-20 | GSE52522 | GEO