Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pancreatic innervation in mouse development and beta-cell regeneration.

ABSTRACT: Pancreatic innervation is being viewed with increasing interest with respect to pancreatic disease. At the same time, relatively little is currently known about innervation dynamics during development and disease. The present study employs confocal microscopy to analyze the growth and development of sympathetic and sensory neurons and astroglia during pancreatic organogenesis and maturation. Our research reveals that islet innervation is closely linked to the process of islet maturation-neural cell bodies undergo intrapancreatic migration/shuffling in tandem with endocrine cells, and close neuro-endocrine contacts are established quite early in pancreatic development. In addition, we have assayed the effects of large-scale beta-cell loss and repopulation on the maintenance of islet innervation with respect to particular neuron types. We demonstrate that depletion of the beta-cell population in the rat insulin promoter (RIP)-cmyc(ER) mouse line has cell-type-specific effects on postganglionic sympathetic neurons and pancreatic astroglia. This study contributes to a greater understanding of how cooperating physiological systems develop together and coordinate their functions, and also helps to elucidate how permutation of one organ system through stress or disease can specifically affect parallel systems in an organism.

SUBMITTER: Burris RE

PROVIDER: S-EPMC2245866 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Decoding pancreatic endocrine cell differentiation and β cell regeneration in zebrafish.

Project description:In contrast to mice, zebrafish have an exceptional yet elusive ability to replenish lost β cells in adulthood. Understanding this framework would provide mechanistic insights for β cell regeneration, which may be extrapolated to humans. Here, we characterize a krt4-expressing ductal cell type, which is distinct from the putative Notch-responsive cells, showing neogenic competence and giving rise to the majority of endocrine cells during postembryonic development. Furthermore, we demonstrate a marked ductal remodeling process featuring a Notch-responsive to krt4+ luminal duct transformation during late development, indicating several origins of krt4+ ductal cells displaying similar transcriptional patterns. Single-cell transcriptomics upon a series of time points during β cell regeneration unveil a previously unrecognized dlb+ transitional endocrine precursor cell, distinct regulons, and a differentiation trajectory involving cellular shuffling through differentiation and dedifferentiation dynamics. These results establish a model of zebrafish pancreatic endocrinogenesis and highlight key values of zebrafish for translational studies of β cell regeneration.

| S-EPMC10438462 | biostudies-literature

HIF1α and pancreatic β-cell development.

Project description:During early embryogenesis, the pancreas shows a paucity of blood flow, and oxygen tension, the partial pressure of oxygen (pO(2)), is low. Later, the blood flow increases as β-cell differentiation occurs. We have previously reported that pO(2) controls β-cell development in rats. Here, we checked that hypoxia inducible factor 1α (HIF1α) is essential for this control. First, we demonstrated that the effect of pO(2) on β-cell differentiation in vitro was independent of epitheliomesenchymal interactions and that neither oxidative nor energetic stress occurred. Second, the effect of pO(2) on pancreas development was shown to be conserved among species, since increasing pO(2) to 21 vs. 3% also induced β-cell differentiation in mouse (7-fold, P<0.001) and human fetal pancreas. Third, the effect of hypoxia was mediated by HIF1α, since the addition of an HIF1α inhibitor at 3% O(2) increased the number of NGN3-expressing progenitors as compared to nontreated controls (9.2-fold, P<0.001). In contrast, when we stabilized HIF1α by deleting ex vivo the gene encoding pVHL in E13.5 pancreas from Vhl floxed mice, Ngn3 expression and β-cell development decreased in such Vhl-deleted pancreas compared to controls (2.5 fold, P<0.05, and 6.6-fold, P<0.001, respectively). Taken together, these data demonstrate that HIF1α exerts a negative control over β-cell differentiation.

| S-EPMC4046099 | biostudies-literature

Mouse strains and sexual divergence in corneal innervation and nerve regeneration.

Project description:A variety of mouse strains and sexes are used in studies of corneal wound healing and nerve regeneration. However, there is a gap of knowledge about corneal nerve density and its function in different mouse strains and sexes. In this study, we report a strain divergence of total and substance P (SP) sensory corneal nerves in uninjured mice. The BALB/c mouse showed the highest nerve density, corneal sensitivity, and tear volume followed by CFW and then C57BL/6. No differences were found in total nerves and SP-positive nerves between sexes. After injury damaged the corneal nerves, an important role for mouse strains, biologic sex, and their association to corneal nerve regeneration was identified. All female mice have a faster nerve regeneration rate than males. The molecular mechanism of this sexual divergence involves higher secretion neurotrophic factors in tears, which in turn modulate gene expression in trigeminal ganglion neurons. An important upstream signaling regulator was β-estradiol, and topical treatment with β-estradiol confirmed its function in corneal nerve regeneration. In conclusion, our study shows that the strain and sex of laboratory mice significantly affect the different indicators of corneal innervation and nerve regeneration. Researchers investigating corneal diseases should carefully consider these factors.-Pham, T. L., Kakazu, A., He, J., Bazan, H. E. P. Mouse strains and sexual divergence in corneal innervation and nerve regeneration.

| S-EPMC6404582 | biostudies-literature

TBK1 regulates regeneration of pancreatic β-cells.

Project description:Small-molecule inhibitors of non-canonical IκB kinases TANK-binding kinase 1 (TBK1) and IκB kinase ε (IKKε) have shown to stimulate β-cell regeneration in multiple species. Here we demonstrate that TBK1 is predominantly expressed in β-cells in mammalian islets. Proteomic and transcriptome analyses revealed that genetic silencing of TBK1 increased expression of proteins and genes essential for cell proliferation in INS-1 832/13 rat β-cells. Conversely, TBK1 overexpression decreased sensitivity of β-cells to the elevation of cyclic AMP (cAMP) levels and reduced proliferation of β-cells in a manner dependent on the activity of cAMP-hydrolyzing phosphodiesterase 3 (PDE3). While the mitogenic effect of (E)3-(3-phenylbenzo[c]isoxazol-5-yl)acrylic acid (PIAA) is derived from inhibition of TBK1, PIAA augmented glucose-stimulated insulin secretion (GSIS) and expression of β-cell differentiation and proliferation markers in human embryonic stem cell (hESC)-derived β-cells and human islets. TBK1 expression was increased in β-cells upon diabetogenic insults, including in human type 2 diabetic islets. PIAA enhanced expression of cell cycle control molecules and β-cell differentiation markers upon diabetogenic challenges, and accelerated restoration of functional β-cells in streptozotocin (STZ)-induced diabetic mice. Altogether, these data suggest the critical function of TBK1 as a β-cell autonomous replication barrier and present PIAA as a valid therapeutic strategy augmenting functional β-cells.

| S-EPMC7653919 | biostudies-literature

Phosphoproteome of mouse pancreatic beta cell

Project description:TMT-labeled phosphoproteome data of mouse pancreatic beta cell

2021-05-11 | PXD022745 | JPOST Repository

Maternal embryonic leucine zipper kinase regulates pancreatic ductal, but not β-cell, regeneration.

Project description:The maternal embryonic leucine zipper kinase (MELK) is expressed in stem/progenitor cells in some adult tissues, where it has been implicated in diverse biological processes, including the control of cell proliferation. Here, we described studies on its role in adult pancreatic regeneration in response to injury induced by duct ligation and β-cell ablation. MELK expression was studied using transgenic mice expressing GFP under the control of the MELK promoter, and the role of MELK was studied using transgenic mice deleted in the MELK kinase domain. Pancreatic damage was initiated using duct ligation and chemical beta-cell ablation. By tracing MELK expression using a MELK promoter-GFP transgene, we determined that expression was extremely low in the normal pancreas. However, following duct ligation and β-cell ablation, it became highly expressed in pancreatic ductal cells while remaining weakly expressed in α-cells and β- cells. In a mutant mouse in which the MELK kinase domain was deleted, there was no effect on pancreatic development. There was no apparent effect on islet regeneration, either. However, following duct ligation there was a dramatic increase in the number of small ducts, but no change in the total number of duct cells or duct cell proliferation. In vitro studies indicated that this was likely due to a defect in cell migration. These results implicate MELK in the control of the response of the pancreas to injury, specifically controlling cell migration in normal and transformed pancreatic duct cells.

| S-EPMC4270240 | biostudies-literature

Silk Fibroin Promotes the Regeneration of Pancreatic β-Cells in the C57BL/KsJ-Leprdb/db Mouse.

Project description:Diabetes mellitus is a chronic metabolic disease, and its progression leads to serious complications. Although various novel therapeutic approaches for diabetes mellitus have developed in the last three decades, its prevalence has been rising more rapidly worldwide. Silk-related materials have been used as anti-diabetic remedies in Oriental medicine and many studies have shown the effects of silk fibroin (SF) in both in vitro and in vivo models. In our previous works, we reported that hydrolyzed SF improved the survival of HIT-T15 cells under high glucose conditions and ameliorated diabetic dyslipidemia in a mouse model. However, we could not provide a precise molecular mechanism. To further evaluate the functions of hydrolyzed SF on the pancreatic β-cell, we investigated the effects of hydrolyzed SF on the pancreatic β-cell proliferation and regeneration in the mouse model. Hydrolyzed SF induced the expression of the proliferating cell nuclear antigen (PCNA) and reduced the apoptotic cell population in the pancreatic islets. Hydrolyzed SF treatment not only induced the expression of transcription factors involved in the pancreatic β-cell regeneration in RT-PCR results but also increased neurogenin3 and Neuro D protein levels in the pancreas of those in the group treated with hydrolyzed SF. In line with this, hydrolyzed SF treatment generated insulin mRNA expressing small cell colonies in the pancreas. Therefore, our results suggest that the administration of hydrolyzed SF increases the pancreatic β-cell proliferation and regeneration in C57BL/KsJ-Leprdb/db mice.

| S-EPMC7397053 | biostudies-literature

Beta cell regeneration after single-round immunological destruction in a mouse model.

Project description:Achieving a better understanding of beta cell regeneration after immunological destruction is crucial for the development of immunotherapy approaches for type 1 diabetes. In previous type 1 diabetes models, sustained immune activation eliminates regenerating beta cells, thus limiting the study of the regenerative capacity of beta cells upon immunological destruction. Here, we employed an adeno-associated virus 8 (AAV8) vector for beta cell-targeted overexpression of a foreign antigen to induce single-round immunological destruction of existing beta cells.Young and aged C57BL/6J mice were treated with AAV8 vectors expressing the foreign antigen luciferase. Islet inflammation and regeneration was observed at 3, 6, 10 and 22 weeks post-AAV delivery.In young C57BL/6J mice, robust humoral and cellular immune responses were developed towards antigen-expressing beta cells, leading to decreased beta cell mass. This was followed by beta cell mass replenishment, along with enhanced proliferation of insulin-positive cells, recruitment of nestin/CD34-positive endothelial cells, displacement of alpha cells and mobilisation of cytoplasmic neurogenin 3-positive cells. Mice with recovering beta cells showed normal or reduced fasting blood glucose levels and faster glucose clearance than controls. Although aged mice demonstrated similar responses to the treatment, they initially exhibited notable islet scarring and fluctuations in blood glucose levels, indicating that beta cell regeneration is slower in aged mice.Our hit-and-run, beta cell-targeted antigen expression system provides an opportunity to monitor the impact of single-round immunological beta cell destruction in animals with diverse genetic backgrounds or ageing status.

| S-EPMC4287683 | biostudies-literature

Postnatal Development and Distribution of Sympathetic Innervation in Mouse Skeletal Muscle.

Project description:Vertebrate neuromuscular junctions (NMJs) have been conceived as tripartite synapses composed of motor neuron, Schwann cell, and muscle fiber. Recent work has shown the presence of sympathetic neurons in the immediate vicinity of NMJs and experimental and clinical findings suggest that this plays an eminent role in adult NMJ biology. The present study examined the postnatal development and distribution of sympathetic innervation in different muscles using immunofluorescence, confocal microscopy, and Western blot. This demonstrates the proximity of sympathetic neurons in diaphragm, extensor digitorum longus, tibialis anterior, soleus, and levator auris longus muscles. In extensor digitorum longus muscle, sympathetic innervation of NMJs was quantified from perinatal to adult stage and found to increase up to two months of age. In diaphragm muscle, an extensive network of sympathetic neurons was prominent along the characteristic central synapse band. In summary, these data demonstrate that an elaborate sympathetic innervation is present in several mouse skeletal muscles and that this is often next to NMJs. Although the presence of sympathetic neurons at the perisynaptic region of NMJs increased during postnatal development, many synapses were already close to sympathetic neurons at birth. Potential implications of these findings for treatment of neuromuscular diseases are discussed.

| S-EPMC6073285 | biostudies-literature

Zebrafish sox9b is crucial for hepatopancreatic duct development and pancreatic endocrine cell regeneration.

Project description:Recent zebrafish studies have shown that the late appearing pancreatic endocrine cells are derived from pancreatic ducts but the regulatory factors involved are still largely unknown. Here, we show that the zebrafish sox9b gene is expressed in pancreatic ducts where it labels the pancreatic Notch-responsive cells previously shown to be progenitors. Inactivation of sox9b disturbs duct formation and impairs regeneration of beta cells from these ducts in larvae. sox9b expression in the midtrunk endoderm appears at the junction of the hepatic and ventral pancreatic buds and, by the end of embryogenesis, labels the hepatopancreatic ductal system as well as the intrapancreatic and intrahepatic ducts. Ductal morphogenesis and differentiation are specifically disrupted in sox9b mutants, with the dysmorphic hepatopancreatic ducts containing misdifferentiated hepatocyte-like and pancreatic-like cells. We also show that maintenance of sox9b expression in the extrapancreatic and intrapancreatic ducts requires FGF and Notch activity, respectively, both pathways known to prevent excessive endocrine differentiation in these ducts. Furthermore, beta cell recovery after specific ablation is severely compromised in sox9b mutant larvae. Our data position sox9b as a key player in the generation of secondary endocrine cells deriving from pancreatic ducts in zebrafish.

| S-EPMC3364407 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data