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Hnf1a mutation in insulin producing beta-cells affect cell function and identity in adult mice

ABSTRACT: Purpose: Hnf1a is an important regulator of pancreas development. Mutation in this gene in humans lead to Maturity Onset Diabetes of the Young 3. Previous studies have shown that Hnf1a is important in function of insulin producing cells. However, they have not payed attention to islet cell identity, which we have focused on. Methods: Male WT mice or mice carrying either a single (htz) or both (hmz) floxed alles of the Hnf1a gene specifically in insulin producing beta-cells controlled by RIP-cre were maintainted in normal housing condition and glyceamia were monitored twice a week. Islet cells were isolated from 12 or 24 weeks old mice of each group and mRNA were extracted before shipping to Qiagen for analysis. Results: Mice carrying the floxed Hnf1a in beta-cells were mildly hyperglyceamic with alterations in expression of important cell identiy genes, potentially more sever with age.

ORGANISM(S): Mus musculus

PROVIDER: GSE193327 | GEO | 2025/12/30

REPOSITORIES: GEO

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	GSE193327_20633_Expression_Browser_12w_HMZvsHTZ.xlsx	Xlsx
	GSE193327_20633_Expression_Browser_12w_HMZvsWT.xlsx	Xlsx
	GSE193327_20633_Expression_Browser_12w_HTZvsWT.xlsx	Xlsx
	GSE193327_20633_Expression_Browser_24w_HMZvsHTZ.xlsx	Xlsx

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Hnf1a mutation in insulin producing beta-cells affect cell function and identity in young and old mice

Project description:Purpose: Hnf1a is an important regulator of pancreas development. Mutation in this gene in humans lead to Maturity Onset Diabetes of the Young 3. Previous studies have shown that Hnf1a is important in function of insulin producing cells. However, they have not payed attention to islet cell identity, which we have focused on. Methods: Male WT mice or mice carrying either a single (htz) or both (hmz) floxed alles of the Hnf1a gene specifically in insulin producing beta-cells controlled by RIP-cre were maintainted in normal housing condition and glyceamia were monitored twice a week. Islet cells were isolated from 6 or 40 weeks old mice of each group and mRNA were extracted before shipping to Qiagen for analysis. Results: Mice carrying the floxed Hnf1a in beta-cells were mildly hyperglyceamic with alterations in expression of important cell identiy genes, potentially more sever with age.

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Ageing signatures in NSG mice

Project description:Purpose: Understanding the role of an active immunesystem in ageing. Methods: Male NSG (NOD scid gamma) immunodeficient mice were maintained in normal housing condition. Islet cells were isolated at different age points and mRNA were extracted before shipping to Qiagen for analysis. Results: In NSG mice multiple of the metabolic pathways that are observed to be deregulated in ageing immunocompotent mice are infered to be sustained.

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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.

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HNF1A regulates a β-cell RNA splicing program that is disrupted in type 2 diabetes [RNA-seq]

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