Importance of multiple endocrine cell types in islet organoids for type 1 diabetes treatment

Heaton, Emma S; Jin, Sha

doi:10.1016/j.trsl.2022.06.014

Cited by 12 publications

(17 citation statements)

References 157 publications

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“…The results, shown for Reactome pathways in Figure 4B depict the most statistically significant terms that were up-regulated in the islets (red) and down-regulated (blue). Confirming the role of the islet cell in insulin signaling 60 , we see regulation of insulin secretion as one of the most enriched pathways in the islet cells. We also observed enrichment in RNA splicing 61,62 and pre mRNA capping as up-regulated.…”

Section: Resultssupporting

confidence: 53%

“…This protein is implicated in the network as an interactor of many highly expressed proteins including Insulin, Glucagon, and Islet amyloid peptide. Despite be-ing a clear regulator of these proteins 60 Insulin-degrading enzyme, while somewhat downregulated (but not statistically so) in the islets, is essential for the regulation of these proteins and therefore belongs in the signaling network. Similarly, we found key proteins that interact with the insulin receptor, which is up-regulated in the acinar tissue ( Figure 5D ).…”

Section: Resultsmentioning

confidence: 98%

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Proteome mapping of the human pancreatic islet microenvironment reveals endocrine-exocrine signaling sphere of influence

Gosline¹,

Veličković²,

Pino³

et al. 2022

Preprint

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The need for a clinically accessible method with the ability to match protein activity within heterogeneous tissues is currently unmet by existing technologies. Our proteomics sample preparation platform, named microPOTS (Microdroplet Processing in One pot for Trace Samples), can be used to measure relative protein abundance in micron-scale samples alongside the spatial location of each measurement, thereby tying biologically interesting proteins and pathways to distinct regions. However, given the smaller sample number and amount of tissue measu red, standard mass spectrometric analysis pipelines have proven inadequate. Here we describe how existing computational approaches can be adapted to focus on the specific biological questions asked in spatial proteomics experiments. We apply this approach to present an unbiased characterization of the human islet microenvironment comprising the entire complex array of tissues involved while maintaining spatial information and the degree of the islet's sphere of influence. We identify specific functional activity unique to the pancreatic islet cells and demonstrate how far their signature can be measured. Our results show that we can distinguish pancreatic islet cells from the neighboring exocrine tissue environment, recapitulate known biological functions of islet cells, and identify a spatial gradient in the expression of RNA processing proteins within the islet microenvironment.

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Section: Resultssupporting

confidence: 53%

Section: Resultsmentioning

confidence: 98%

Proteome mapping of the human pancreatic islet microenvironment reveals endocrine-exocrine signaling sphere of influence

Gosline¹,

Veličković²,

Pino³

et al. 2022

Preprint

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show abstract

“…The SC‐islets consisted of >66% insulin‐positive cells, >17% somatostatin‐positive cells, and >22% glucagon‐positive cells, whereas >95% of the cells were endocrine cells (i.e., cells which can secrete hormones). The multicellular SC‐islets have a composition, which is similar to the distribution of the cell types in human islets [13, 15].…”

Section: Resultsmentioning

confidence: 99%

“…Stem cell-derived pancreatic islet organoids (SC-islets) are an emerging alternative for disease modeling of diabetes and cell replacement therapy [12,13]. Similar to natural islets, SC-islets differentiated from embryonic stem cells consist of multiple types of endocrine cells [14,15]. SC-islets should therefore be suitable for disease modeling and may serve as a source for islet transplantation in betacell replacement therapy for type 1 diabetes patients [13,15].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous LC–MS determination of glucose regulatory peptides secreted by stem cell–derived islet organoids

et al. 2023

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For studying stem cell–derived islet organoids (SC‐islets) in an organ‐on‐chip (OoC) platform, we have developed a reversed‐phase liquid chromatography–tandem mass spectrometry (RPLC–MS/MS) method allowing for simultaneous determination of insulin, somatostatin‐14, and glucagon, with improved matrix robustness compared to earlier methodology. Combining phenyl/hexyl‐C18 separations using 2.1 mm inner diameter LC columns and triple quadrupole mass spectrometry, identification and quantification were secured with negligible variance in retention time and quantifier/qualifier ratios, negligible levels of carryover (<2%), and sufficient precision (±10% RSD) and accuracy (±15% relative error) with and without use of an internal standard. The obtained lower limits of quantification were 0.2 µg/L for human insulin, 0.1 µg/L for somatostatin‐14, and 0.05 µg/L for glucagon. The here‐developed RPLC–MS/MS method showed that the SC‐islets have an insulin response dependent on glucose concentration, and the SC‐islets produce and release somatostatin‐14 and glucagon. The RPLC–MS/MS method for these peptide hormones was compatible with an unfiltered offline sample collection from SC‐islets cultivated on a pumpless, recirculating OoC (rOoC) platform. The SC‐islets background secretion of insulin was not significantly different on the rOoC device compared to a standard cell culture well‐plate. Taken together, RPLC–MS/MS method is well suited for multi‐hormone measurements of SC‐islets on an OoC platform.

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“…7,8 Meanwhile, islet isolation disrupts other islet-resident nonhormonal cells, such as endothelial cells and mesenchymal cells, which support endocrine cell function. 9,10 To address this challenge, there is an urgent need to improve the transplantation method for islet delivery, immune modulation, the site of transplantation, and transplanted islet revascularization.…”

Section: Introductionmentioning

confidence: 99%

Construction of engineered 3D islet micro-tissue using porcine decellularized ECM for the treatment of diabetes

et al. 2023

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Importance of multiple endocrine cell types in islet organoids for type 1 diabetes treatment

Cited by 12 publications

References 157 publications

Proteome mapping of the human pancreatic islet microenvironment reveals endocrine-exocrine signaling sphere of influence

Proteome mapping of the human pancreatic islet microenvironment reveals endocrine-exocrine signaling sphere of influence

Simultaneous LC–MS determination of glucose regulatory peptides secreted by stem cell–derived islet organoids

Construction of engineered 3D islet micro-tissue using porcine decellularized ECM for the treatment of diabetes

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