Single-cell gene expression and chromatin accessibility profiling of human pancreatic islets at basal and stimulatory conditions nominates mechanisms of type 1 diabetes genetic risk

Albanus, Ricardo D’Oliveira; Tang, Xiaoxue; Taylor, Henry J.; Manickam, Nandini; Erdos, Michael R.; Narisu, Narisu; Han, Yanxiao; Orchard, Peter; Varshney, Arushi; Liu, Chengyang; Naji, Ali; Collins, Francis S.; Chen, Shuibing; Parker, Stephen C. J.

doi:10.1101/2022.11.12.516291

Cited by 3 publications

(1 citation statement)

References 62 publications

(85 reference statements)

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“…These overlaps included variants at loci highly associated with human diabetes, including FTO ( 161, 162 ), IGF2BP2 ( 163, 164 ), CMIP ( 165, 166 ), and VPS13C ( 167, 168 ). In addition, we are able to identify peak overlap with novel human diabetes variants like rs1947178, which is located 159,430 bp downstream of the TOX transcription start site (TSS) and is predicted to increase chromatin accessibility and gene expression of TOX , a transcriptional regulator in T1D ( 169 ). We observed increased accessibility in fruit bats in this region, along with upregulation of TOX in fruit bat beta, alpha, acinar-i and acinar-s cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Integrative single-cell characterization of frugivory adaptations in the bat kidney and pancreas

Gordon

Baek

Nguyen

et al. 2023

Preprint

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Frugivory evolved multiple times in mammals, including bats. However, the cellular and molecular components driving it remain largely unknown. Here, we used integrative single-cell sequencing on insectivorous and frugivorous bat kidneys and pancreases and identified key cell population, gene expression and regulatory element differences associated with frugivorous adaptation that also relate to human disease, particularly diabetes. We found an increase in collecting duct cells and differentially active genes and regulatory elements involved in fluid and electrolyte balance in the frugivore kidney. In the frugivorous pancreas, we observed an increase in endocrine and a decrease in exocrine cells and differences in genes and regulatory elements involved in insulin regulation. Combined, our work provides novel insights into frugivorous adaptation that also could be leveraged for therapeutic purposes.

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Section: Resultsmentioning

confidence: 99%

Integrative single-cell characterization of frugivory adaptations in the bat kidney and pancreas

Gordon

Baek

Nguyen

et al. 2023

Preprint

View full text Add to dashboard Cite

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Integrative single-cell characterization of a frugivorous and an insectivorous bat kidney and pancreas

Gordon,

Baek,

Nguyen

et al. 2024

Nat Commun

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Frugivory evolved multiple times in mammals, including bats. However, the cellular and molecular components driving it remain largely unknown. Here, we use integrative single-cell sequencing (scRNA-seq and scATAC-seq) on insectivorous (Eptesicus fuscus; big brown bat) and frugivorous (Artibeus jamaicensis; Jamaican fruit bat) bat kidneys and pancreases and identify key cell population, gene expression and regulatory differences associated with the Jamaican fruit bat that also relate to human disease, particularly diabetes. We find a decrease in loop of Henle and an increase in collecting duct cells, and differentially active genes and regulatory elements involved in fluid and electrolyte balance in the Jamaican fruit bat kidney. The Jamaican fruit bat pancreas shows an increase in endocrine and a decrease in exocrine cells, and differences in genes and regulatory elements involved in insulin regulation. We also find that these frugivorous bats share several molecular characteristics with human diabetes. Combined, our work provides insights from a frugivorous mammal that could be leveraged for therapeutic purposes.

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An integrated map of cell type-specific gene expression in pancreatic islets

Elgamal

Kudtarkar

Melton

et al. 2023

Preprint

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Pancreatic islets are comprised of multiple endocrine cell types that produce hormones required for glucose homeostasis, and islet dysfunction is a major factor in the development of type 1 and type 2 diabetes (T1D, T2D). Numerous studies have generated gene expression profiles in individual islet cell types using single cell assays. However, there is no canonical reference of gene expression in islet cell types in both health and disease that is also easily accessible for researchers to access, query, and use in bioinformatics pipelines. Here we present an integrated reference map of islet cell type-specific gene expression from 192,203 cells derived from single cell RNA-seq assays of 65 non-diabetic, T1D autoantibody positive (Aab+), T1D, and T2D donors from the Human Pancreas Analysis Program. We identified 10 endocrine and non-endocrine cell types as well as sub-populations of several cell types, and defined sets of marker genes for each cell type and sub-population. We tested for differential expression within each cell type in T1D Aab+, T1D, and T2D states, and identified 1,701 genes with significant changes in expression in any cell type. Most changes were observed in beta cells in T1D, and, by comparison, there were almost no genes with changes in T1D Aab+. To facilitate user interaction with this reference, we provide the data using several single cell visualization and reference mapping tools as well as open-access analytical pipelines used to create this reference. The results will serve as a valuable resource to investigators studying islet biology and diabetes.

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Single-cell gene expression and chromatin accessibility profiling of human pancreatic islets at basal and stimulatory conditions nominates mechanisms of type 1 diabetes genetic risk

Cited by 3 publications

References 62 publications

Integrative single-cell characterization of frugivory adaptations in the bat kidney and pancreas

Integrative single-cell characterization of frugivory adaptations in the bat kidney and pancreas

Integrative single-cell characterization of a frugivorous and an insectivorous bat kidney and pancreas

An integrated map of cell type-specific gene expression in pancreatic islets

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