Whole‐Mount Imaging Demonstrates Hypervascularity of the Pancreatic Ducts and Other Pancreatic Structures

El-Gohary, Yousef; Tulachan, Sidhartha; Branca, Maria F.; Sims‐Lucas, Sunder; Guo, Ping; Prasadan, Krishna; Shiota, Chiyo; Gittes, George K.

doi:10.1002/ar.22420

Cited by 15 publications

(15 citation statements)

References 28 publications

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“…This approach, especially in combination with whole-mount imaging, provides an excellent appreciation of pancreatic ductal anatomy and labeling efficiency in the mouse pancreas. 30,31 In conclusion, AAV6-mediated tissue tropism, combined with a sox9 shorter promoter and direct intraductal viral delivery can achieve durable and specific pancreatic duct tagging. This method, along with whole-mount imaging, should complement existing methods for the study of pancreatic duct lineages.…”

Section: Discussionmentioning

confidence: 91%

“…28 Whole-Mount Staining and Immunohistochemistry Whole-mount immunofluorescence staining was carried out as described previously. [29][30][31] In brief, mice were infused with 10 ml PBS, followed by 10 ml 4% paraformaldehyde (PFA). The pancreatic tissues were then harvested and fixed in 4% PFA for 2 h in 4 1C.…”

Section: Generation and Purification Of Aav Serotype 6 Virusesmentioning

confidence: 99%

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Specific transduction and labeling of pancreatic ducts by targeted recombinant viral infusion into mouse pancreatic ducts

Guo

Xiao

El-Gohary

et al. 2013

Laboratory Investigation

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Specific labeling of pancreatic ducts has proven to be quite difficult. Such labeling has been highly sought after because of the power it would confer to studies of pancreatic ductal carcinogenesis, as well as studies of the source of new insulinproducing b-cells. Cre-loxp recombination could, in theory, lineage-tag pancreatic ducts, but results have been conflicting, mainly due to low labeling efficiencies. Here, we achieved a high pancreatic duct labeling efficiency using a recombinant adeno-associated virus (rAAV) with a duct-specific sox9 promoter infused into the mouse common biliary/pancreatic duct. We saw rapid, diffuse duct-specific labeling, with 50 and 89% labeling in the pancreatic tail and head region, respectively. This highly specific labeling of ducts should greatly enhance our ability to study the role of pancreatic ducts in numerous aspects of pancreatic growth, development and function.

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Section: Discussionmentioning

confidence: 91%

Section: Generation and Purification Of Aav Serotype 6 Virusesmentioning

confidence: 99%

Specific transduction and labeling of pancreatic ducts by targeted recombinant viral infusion into mouse pancreatic ducts

Guo

Xiao

El-Gohary

et al. 2013

Laboratory Investigation

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“…As in the fish, rodent CACs proliferate in response to pancreas injury (Gasslander et al, 1992; Hayashi et al, 1999; Hayashi et al, 2003). Several other studies have observed endocrine cells near to or embedded in the ductal tree during normal growth or regeneration (Bonner-Weir et al, 1993; El-Gohary et al, 2012; Gu and Sarvetnick, 1993; Li et al, 2010; Phillips et al, 2007; Rooman and Bouwens, 2004; Rosenberg, 1995; Weaver et al, 1985; Xu et al, 1999; Xu et al, 2008; Yoneda et al, 2013). Indeed, Ngn3-positive cells lining the ducts contribute to β cell expansion induced by overexpressing Pax4 in α cells (Al-Hasani et al, 2013).…”

Section: Centroacinar Cells As Adult Progenitorsmentioning

confidence: 94%

Centroacinar cells: At the center of pancreas regeneration

Beer

Parsons

Rovira

2016

Developmental Biology

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The process of regeneration serves to heal injury by replacing missing cells. Understanding regeneration can help us replace cell populations lost during disease, such as the insulin-producing β cells lost in diabetic patients. Centroacinar cells (CACs) are a specialized ductal pancreatic cell type that act as progenitors to replace β cells in the zebrafish. However, whether CACs contribute to β-cell regeneration in adult mammals remains controversial. Here we review the current understanding of the role of CACs as endocrine progenitors during regeneration in zebrafish and mammals.

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“…β-cell replication (1,2) and neogenesis (3–5) are the two main mechanisms that have been proposed for the formation of new β-cells. β-cell replication is generally accepted as the predominant mechanism for the generation of new β-cells in the adult islet (1), but it remains unclear how such a terminally differentiated cell can undergo proliferation (6).…”

Section: Introductionmentioning

confidence: 99%

A Smad Signaling Network Regulates Islet Cell Proliferation

et al. 2013

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Pancreatic β-cell loss and dysfunction are critical components of all types of diabetes. Human and rodent β-cells are able to proliferate, and this proliferation is an important defense against the evolution and progression of diabetes. Transforming growth factor-β (TGF-β) signaling has been shown to affect β-cell development, proliferation, and function, but β-cell proliferation is thought to be the only source of new β-cells in the adult. Recently, β-cell dedifferentiation has been shown to be an important contributory mechanism to β-cell failure. In this study, we tie together these two pathways by showing that a network of intracellular TGF-β regulators, smads 7, 2, and 3, control β-cell proliferation after β-cell loss, and specifically, smad7 is necessary for that β-cell proliferation. Importantly, this smad7-mediated proliferation appears to entail passing through a transient, nonpathologic dedifferentiation of β-cells to a pancreatic polypeptide–fold hormone-positive state. TGF-β receptor II appears to be a receptor important for controlling the status of the smad network in β-cells. These studies should help our understanding of properly regulated β-cell replication.

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Whole‐Mount Imaging Demonstrates Hypervascularity of the Pancreatic Ducts and Other Pancreatic Structures

Cited by 15 publications

References 28 publications

Specific transduction and labeling of pancreatic ducts by targeted recombinant viral infusion into mouse pancreatic ducts

Specific transduction and labeling of pancreatic ducts by targeted recombinant viral infusion into mouse pancreatic ducts

Centroacinar cells: At the center of pancreas regeneration

A Smad Signaling Network Regulates Islet Cell Proliferation

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