Robert A. Piscopio

Optogenetic Rescue Reveals Spatiotemporal Rules of Germ-Layer Patterning

Naomi J. Baxter, Robert A. Piscopio, Joseph Rufo, Dasol Han et autres

Embryonic cells must interpret morphogen signals that vary in both time and space, but the rules by which they decode these dynamics remain unclear. Here we combine optogenetics with human 2D gastruloids to define minimal WNT signaling rules for germ-layer patterning. We …

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Photolabile oligonucleotides combined with topologically imposed light gradients enable spatially resolved single-cell transcriptomics and epigenomics

Robert A. Piscopio, Alex Chialastri, Chieh Wang, Mikolaj Godzik et autres

The organization of cells within a tissue plays a critical role in tuning cellular function. Several methods have recently been developed to capture the transcriptome of cells while retaining spatial information. However, these genome-wide sequencing methods typically lack the spatial resolution of …

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Cleavage of protein kinase c δ by caspase-3 mediates proinflammatory cytokine-induced apoptosis in pancreatic islets

Jillian Collins, Robert A. Piscopio, Mary E. Reyland, Chelsea G. Johansen et autres

In type 1 diabetes (T1D), autoreactive immune cells infiltrate the pancreas and secrete proinflammatory cytokines that initiate cell death in insulin producing islet β-cells. Protein kinase C δ (PKCδ) plays a role in mediating cytokine-induced β-cell death; however, the exact mechanisms are …

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Optogenetic control of the integrated stress response reveals proportional encoding and the stress memory landscape

Taivan Batjargal, Francesca Zappa, Ryan J. Grant, Robert A. Piscopio et autres

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Functional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium response

Vira V. Kravets, JaeAnn M. Dwulet, Wolfgang E. Schleicher, David J. Hodson et autres

Insulin-secreting β-cells are functionally heterogeneous. Whether there exist cells driving the first-phase calcium response in individual islets, has not been examined. We examine "first responder" cells, defined by the earliest [Ca2+] response during first-phase [Ca2+] elevation, distinct from previously identified "hub" and …

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Cleavage of protein kinase c δ by caspase-3 mediates pro-inflammatory cytokine-induced apoptosis in pancreatic islets

Jillian Collins, Robert A. Piscopio, Mary E. Reyland, Chelsea G. Johansen et autres

Abstract In type 1 diabetes (T1D), autoreactive immune cells infiltrate the pancreas and secrete pro-inflammatory cytokines that initiate cell death in insulin producing islet β-cells. Protein kinase C δ (PKCδ) plays a role in mediating cytokine-induced β-cell death; however, the exact mechanisms …

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Modulation of Gap Junction Coupling Within the Islet of Langerhans During the Development of Type 1 Diabetes

Nikki L. Farnsworth, Robert A. Piscopio, Wolfgang E. Schleicher, David G. Ramirez et autres

In type 1 diabetes (T1D), islet dysfunction occurs prior to diabetes onset. Pro-inflammatory cytokines can disrupt insulin secretion and Ca2+ homeostasis. Connexin36 (Cx36) gap junctions electrically couple β-cells to coordinate glucose-stimulated Ca2+ and insulin secretion. Cx36 gap junction coupling can also protect …

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Optogenetic control of the integrated stress response reveals proportional encoding and the stress memory landscape

Taivan Batjargal, Francesca Zappa, Ryan J. Grant, Robert A. Piscopio et autres

Abstract The Integrated Stress Response (ISR) is a conserved signaling network that detects cellular damage and computes adaptive or terminal outcomes. Understanding the mechanisms that underly these computations has been difficult because natural stress inputs activate multiple parallel signaling pathways and classical …

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Optogenetic Control of the Integrated Stress Response Reveals Proportional Encoding and the Stress Memory Landscape

Taivan Batjargal, Francesca Zappa, Ryan J. Grant, Robert A. Piscopio et autres

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Optogenetic stimulation of cholinergic fibers for the modulation of insulin and glycemia

Arjun K. Fontaine, David G. Ramirez, Samuel F. Littich, Robert A. Piscopio et autres

Previous studies have demonstrated stimulation of endocrine pancreas function by vagal nerve electrical stimulation. While this increases insulin secretion, expected concomitant reductions in circulating glucose do not occur. A complicating factor is the non-specific nature of electrical nerve stimulation. Optogenetic tools, however, …

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Functional architecture of the pancreatic islets reveals first responder cells which drive the first-phase [Ca 2+ ] response

Vira V. Kravets, JaeAnn M. Dwulet, Wolfgang E. Schleicher, David J. Hodson et autres

Abstract Insulin-secreting β-cells are functionally heterogeneous. Whether there exist cells driving the first-phase calcium response in individual islets, has not been examined. We examine ‘first responder’ cells, defined by the earliest [Ca 2+ ] response during first-phase [Ca 2+ ] elevation, distinct …

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Caloric restriction recovers impaired β-cell-β-cell gap junction coupling, calcium oscillation coordination, and insulin secretion in prediabetic mice

Maria Esméria Corezola do Amaral, Vira V. Kravets, JaeAnn M. Dwulet, Nikki L. Farnsworth et autres

Caloric restriction can decrease the incidence of metabolic diseases, such as obesity and Type 2 diabetes mellitus. The mechanisms underlying the benefits of caloric restriction involved in insulin secretion and glucose homeostasis are not fully understood. Intercellular communication within the islets of …

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