β‐Cell evolution: How the pancreas borrowed from the brain

Arntfield, Margot; Kooy, Derek van der

doi:10.1002/bies.201100015

Cited by 85 publications

(38 citation statements)

References 74 publications

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“…PP cells have substantial expression of genes related to neuronal cells, which hints at the developmental proximity of PP and neuronal cells. This has been previously described by others in the context of beta cells (Arntfield and van der Kooy, 2011, Le Roith et al., 1982)…”

Section: Resultssupporting

confidence: 74%

A Single-Cell Transcriptome Atlas of the Human Pancreas

et al. 2016

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SummaryTo understand organ function, it is important to have an inventory of its cell types and of their corresponding marker genes. This is a particularly challenging task for human tissues like the pancreas, because reliable markers are limited. Hence, transcriptome-wide studies are typically done on pooled islets of Langerhans, obscuring contributions from rare cell types and of potential subpopulations. To overcome this challenge, we developed an automated platform that uses FACS, robotics, and the CEL-Seq2 protocol to obtain the transcriptomes of thousands of single pancreatic cells from deceased organ donors, allowing in silico purification of all main pancreatic cell types. We identify cell type-specific transcription factors and a subpopulation of REG3A-positive acinar cells. We also show that CD24 and TM4SF4 expression can be used to sort live alpha and beta cells with high purity. This resource will be useful for developing a deeper understanding of pancreatic biology and pathophysiology of diabetes mellitus.

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Section: Resultssupporting

confidence: 74%

A Single-Cell Transcriptome Atlas of the Human Pancreas

et al. 2016

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“…Phylogenetic analyses of insulin-producing cells suggest that mammalian β-cells and fly IPCs have common evolutionary origins or have different origins but have undergone convergent evolution (Arntfield and Van Der Kooy 2011). Mammalian β-cells arise from the endoderm (Jensen 2004), and fly IPCs are neurons arising from the ectoderm (Wang et al 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Fly IPCs have long axons requiring extensive transport of vesicles, while β-cells have no axons. Yet phylogenic analyses of insulin-expressing cells indicate that neurons evolved to secrete insulin before there were β-cells, creating a puzzle about the evolutionary origin of β-cells (Arntfield and Van Der Kooy 2011). In jellyfish, insulin is produced only by neurons (Davidson et al 1971).…”

Section: Discussionmentioning

confidence: 99%

Insight into Insulin Secretion from Transcriptome and Genetic Analysis of Insulin-Producing Cells of Drosophila

Cao

et al. 2014

Genetics

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Insulin-producing cells (IPCs) in the Drosophila brain produce and release insulin-like peptides (ILPs) to the hemolymph. ILPs are crucial for growth and regulation of metabolic activity in flies, functions analogous to those of mammalian insulin and insulin-like growth factors (IGFs). To identify components functioning in IPCs to control ILP production, we employed genomic and candidate gene approaches. We used laser microdissection and messenger RNA sequencing to characterize the transcriptome of larval IPCs. IPCs highly express many genes homologous to genes active in insulin-producing β-cells of the mammalian pancreas. The genes in common encode ILPs and proteins that control insulin metabolism, storage, secretion, β-cell proliferation, and some not previously linked to insulin production or β-cell function. Among these novelties is unc-104, a kinesin 3 family gene, which is more highly expressed in IPCs compared to most other neurons. Knockdown of unc-104 in IPCs impaired ILP secretion and reduced peripheral insulin signaling. Unc-104 appears to transport ILPs along axons. As a complementary approach, we tested dominant-negative Rab genes to find Rab proteins required in IPCs for ILP production or secretion. Rab1 was identified as crucial for ILP trafficking in IPCs. Inhibition of Rab1 in IPCs increased circulating sugar levels, delayed development, and lowered weight and body size. Immunofluorescence labeling of Rab1 showed its tight association with ILP2 in the Golgi of IPCs. Unc-104 and Rab1 join other proteins required for ILP transport in IPCs.

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“…This is due, in part, to an evolving realization that beta-cells and neurons possess striking similarities, both functionally and in genetic profile. In 2011 Arntfield and van der Kooy summarized the similarities between neurons and beta-cells and suggested that in an instance of convergent evolution, beta-cells are “borrowed from the brain” (Table 1, [22–44]). Basically, neurons and beta-cells are derived from different tissue layers, ectoderm and endoderm respectively, but are very similar in the way that they store, respond to, and transmit signaling molecules.…”

Section: Borrowed Evolution: Beta-cells and Neuronsmentioning

confidence: 99%

Common defects of mitochondria and iron in neurodegeneration and diabetes (MIND): A paradigm worth exploring

Stroh¹,

Swerdlow²,

Zhu³

2014

Biochemical Pharmacology

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A popular, if not centric, approach to the study of an event is to first consider that of the simplest cause. When dissecting the underlying mechanisms governing idiopathic diseases, this generally takes the form of an ab initio genetic approach. To date, this genetic ‘smoking gun’ has remained elusive in diabetes mellitus and for many affected by neurodegenerative diseases. With no single gene, or even subset of genes, conclusively causative in all cases, other approaches to the etiology and treatment of these diseases seem reasonable, including the correlation of a systems’ predisposed sensitivity to particular influence. In the cases of diabetes mellitus and neurodegenerative diseases, overlapping themes of mitochondrial influence or dysfunction and iron dyshomeostasis are apparent and relatively consistent. This mini-review discusses the influence of mitochondrial function and iron homeostasis on diabetes mellitus and neurodegenerative disease, namely Alzheimer’s disease. Also discussed is the incidence of diabetes accompanied by neuropathy and neurodegeneration along with neurodegenerative disorders prone to development of diabetes. Mouse models containing multiple facets of this overlap are also described alongside current molecular trends attributed to both diseases. As a way of approaching the idiopathic and complex nature of these diseases we are proposing the consideration of a MIND (mitochondria, iron, neurodegeneration, and diabetes) paradigm in which systemic metabolic influence, iron homeostasis, and respective genetic backgrounds play a central role in the development of disease.

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β‐Cell evolution: How the pancreas borrowed from the brain

Abstract: Editor's suggested further reading in BioEssaysA new paradigm in cell therapy for diabetes: Turning pancreatic α‐cells into β‐cells Abstract

Cited by 85 publications

References 74 publications

A Single-Cell Transcriptome Atlas of the Human Pancreas

A Single-Cell Transcriptome Atlas of the Human Pancreas

Insight into Insulin Secretion from Transcriptome and Genetic Analysis of Insulin-Producing Cells of Drosophila

Common defects of mitochondria and iron in neurodegeneration and diabetes (MIND): A paradigm worth exploring

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