miR-184 Regulates Pancreatic β-Cell Function According to Glucose Metabolism

In response to fasting or hyperglycemia, the pancreatic β-cell alters its output of secreted insulin; however, the pathways governing this adaptive response are not entirely established. Although the precise role of microRNAs (miRNAs) is also unclear, a recurring theme emphasizes their function in cellular stress responses. We recently showed that miR-184, an abundant miRNA in the β-cell, regulates compensatory proliferation and secretion during insulin resistance. Consistent with previous studies showing miR-184 suppresses insulin release, expression of this miRNA was increased in islets after fasting, demonstrating an active role in the β-cell as glucose levels lower and the insulin demand ceases. Additionally, miR-184 was negatively regulated upon the administration of a sucrose-rich diet in Drosophila, demonstrating strong conservation of this pathway through evolution. Furthermore, miR-184 and its target Argonaute2 remained inversely correlated as concentrations of extracellular glucose increased, underlining a functional relationship between this miRNA and its targets. Lastly, restoration of Argonaute2 in the presence of miR-184 rescued suppression of miR-375-targeted genes, suggesting these genes act in a coordinated manner during changes in the metabolic context. Together, these results highlight the adaptive role of miR-184 according to glucose metabolism and suggest the regulatory role of this miRNA in energy homeostasis is highly conserved

Argonaute2 Mediates Compensatory Expansion of the Pancreatic β Cell

Pancreatic β cells adapt to compensate for increased metabolic demand during insulin resistance. Although the microRNA pathway has an essential role in β cell proliferation, the extent of its contribution is unclear. Here, we report that miR-184 is silenced in the pancreatic islets of insulin-resistant mouse models and type 2 diabetic human subjects. Reduction of miR-184 promotes the expression of its target Argonaute2 (Ago2), a component of the microRNA-induced silencing complex. Moreover, restoration of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory β cell expansion. Loss of Ago2 during insulin resistance blocked β cell growth and relieved the regulation of miR-375-targeted genes, including the growth suppressor Cadm1. Lastly, administration of a ketogenic diet to ob/ob mice rescued insulin sensitivity and miR-184 expression and restored Ago2 and β cell mass. This study identifies the targeting of Ago2 by miR-184 as an essential component of the compensatory response to regulate proliferation according to insulin sensitivity

Fly Cell Atlas: a single-nucleus transcriptomic atlas of the adult fruit fly

The fruit fly Drosophila melanogaster has served as a premier model organism for discovering fundamental and evolutionarily conserved biological mechanisms. Combining recent advances in single-cell sequencing with powerful fly genetic tools holds great promise for making further discoveries. Li et al. present a single-cell atlas of the entire adult fly that includes 580,000 cells and more than 250 annotated cell types. Cells from the head and body recapitulated cell types from 15 dissected tissues. In-depth analyses revealed rare cell types, cell-type-specific gene signatures, and sexual dimorphism. This atlas provides a resource for the Drosophila community to study genetic perturbations and diseases at single-cell resolution. —BA

Fly Cell Atlas: a single-nucleus transcriptomic atlas of the adult fruit fly

The fruit fly Drosophila melanogaster has served as a premier model organism for discovering fundamental and evolutionarily conserved biological mechanisms. Combining recent advances in single-cell sequencing with powerful fly genetic tools holds great promise for making further discoveries. Li et al. present a single-cell atlas of the entire adult fly that includes 580,000 cells and more than 250 annotated cell types. Cells from the head and body recapitulated cell types from 15 dissected tissues. In-depth analyses revealed rare cell types, cell-type-specific gene signatures, and sexual dimorphism. This atlas provides a resource for the Drosophila community to study genetic perturbations and diseases at single-cell resolution. —BA

Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly.

For more than 100 years, the fruit fly Drosophila melanogaster has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula Drosophilae, that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250 distinct cell types. We provide an in-depth analysis of cell type-related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types between tissues, such as blood and muscle cells, reveals rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the Drosophila community and serves as a reference to study genetic perturbations and disease models at single-cell resolution

Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly

For more than 100 years, the fruit fly Drosophila melanogaster has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula Drosophilae , that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250 distinct cell types. We provide an in-depth analysis of cell type–related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types between tissues, such as blood and muscle cells, reveals rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the Drosophila community and serves as a reference to study genetic perturbations and disease models at single-cell resolution