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Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors

ABSTRACT: Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors

PROVIDER: PRJNA1073578 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27882466_1.fastq.gz	Fastqsanger.gz
	SRR27882466_2.fastq.gz	Fastqsanger.gz
	SRR27882467_1.fastq.gz	Fastqsanger.gz
	SRR27882467_2.fastq.gz	Fastqsanger.gz
	SRR27882468_1.fastq.gz	Fastqsanger.gz

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Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors

Project description:Endocrine islet beta cells comprise heterogenous cell subsets. Yet the origin, stability, and physiological significance of these subsets remain largely unknown. Using combinatorial cell lineage tracing, scRNA-seq, and DNA methylation analysis, we show here that embryonic islet progenitors with differential gene expression and DNA methylation produce stable beta-cell subtypes of different function and viability in adult mice. Differentially expressed genes, including the Myt transcription factors, voltage-gated channels, and Ca2+-sensor synaptotagmins, contribute to the functional differences of these subtypes. Maternal overnutrition, a major diabetes risk factor, reduces the proportion of endocrine progenitors of the better-functionality beta-cell subtype. Intriguingly, the gene signature that defines mouse beta-cell subtypes can reliably divide human cells into two populations, with the proportion of better-functionality beta cells reduced in diabetic donors. These results establish that some beta-cell subtypes are determined via DNA methylation in embryonic islet progenitors, which is regulated by diabetes-causing maternal factors. The implication is that modulating DNA methylation in islet progenitors can be explored to improve beta-cell function in the prevention and therapy of diabetes.

2025-04-22 | GSE255135 | GEO

Endocrine islet beta-cell subtypes with differential function are derived from biochemically distinct embryonic endocrine islet progenitors that are regulated by maternal nutrients

2025-02-01 | GSE254955 | GEO

Endocrine islet beta-cell subtypes with differential function are derived from biochemically distinct embryonic endocrine islet progenitors that are regulated by maternal nutrients

Project description:Endocrine islet beta-cell subtypes with differential function are derived from biochemically distinct embryonic endocrine islet progenitors that are regulated by maternal nutrients

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Molecular and genetic regulation of pig pancreatic islet cell development

Project description:We report the transcriptomic profiling of islet cell subtypes obtained from pigs at different developmental stages

2020-04-01 | GSE143889 | GEO

Robust Differentiation of Islet Progenitors into Functional Insulin-secreting Cells by Suppression of Key Transcription Regulators

Project description:Gene profiling revealed that differentiation was accompanied by suppression of a range of transcription regulator genes typical of islet progenitor cells. In order to understand molecular mechanisms of differentiation, transcriptome-wide gene expression analysis was performed on purified islet progenitors at days 0, 1 and 4 of differentiation together with adult islets as a control. In order to understand molecular mechanisms of differentiation, transcriptome-wide gene expression analysis was performed on purified islet progenitors at days 0, 1 and 4 of differentiation together with adult islets as a control.

2013-11-01 | E-GEOD-51944 | biostudies-arrayexpress

in vivo environment swiftly restricts human pancreatic progenitors towards monohormonal identity via a HNF1A/HNF4A mechanism

Project description:Generating insulin-producing β-cells from human induced pluripotent stem cells is a promising cell replacement therapy aimed at improving or curing certain forms of diabetes. Nevertheless, despite important recent advances, the efficient production of functionally mature β-cells is yet to be achieved, with most current differentiation protocols generating a heterogeneous population comprising of subpopulation of cells expressing different islet hormones, including hybrid polyhormonal entities. A solution to this issue is transplanting end-stages differentiating cells into living hosts, which was demonstrated to majorly improve β-cell maturation. Yet, to date, the cellular and molecular mechanisms underlying the transplanted cells response to the in vivo environment exposure was not yet properly characterized. Here we use global proteomics and large-scale imaging techniques aimed at demultiplexing and filtering cellular processes and molecular signatures modulated by the immediate in vivo effect. We show that in vivo exposure swiftly confines in vitro generated human pancreatic progenitors to single hormone expression. The global proteome landscape of the transplanted cells was closer to the one presented by native human islets, especially in regard to energy metabolism and redox balance. Moreover our study indicates a possible link between these processed and certain epigenetic regulators involved in maintenance and propagation of the islet cells identity. Pathway analysis predicted HNF1A and HNF4A as key regulators controlling the in vivo islet-promoting response, with experimental evidence confirming their involvement in confining islet cell identity. To our knowledge this is the first study demultiplexing the immediate response of the transplanted pancreatic progenitors to in vivo exposure.

2020-02-12 | PXD015955 | Pride

Open chromatin landscape of pancreatic endocrine progenitors

Project description:During embryonic development, islet progenitors are specified from pancreatic duct cells by transient expression of Neurog3, a transcription factor necessary and sufficient for initiation of islet development. To understand the dynamics of Neurog3-dependent endocrine cell fate determination, in this study we used ATAC-Seq to identify accessible genomic regions of purified duct, endocrine progenitor, and endocrine cells isolated from mice with varying Neurog3 dosage

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Retinoic acid signaling within pancreatic endocrine progenitors regulates mouse and human pancreatic islet cell specification

Project description:Retinoic acid signaling within pancreatic endocrine progenitors regulates mouse and human pancreatic islet cell specification

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Single-cell transcriptomics reveals unique features of human pancreatic islet cell subtypes

Project description:We report the single-cell RNA-seq based identification of 6 known human islet cell types (alpha cells, beta cells, delta cells, pp cells, acinar cells and duct cells) based on the expression of known marker genes. We further assess cell type specific gene expression and suggest novel marker genes for several cell types. Transcriptional dissection of human pancreatic islets of one donor using single-cell RNA-seq

2016-01-05 | E-GEOD-73727 | biostudies-arrayexpress

Robust Differentiation of Islet Progenitors into Functional Insulin-secreting Cells by Suppression of Key Transcription Regulators

2013-11-01 | GSE51944 | GEO