The Experts below are selected from a list of 40125 Experts worldwide ranked by ideXlab platform
Bin Liu - One of the best experts on this subject based on the ideXlab platform.
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activation of pyroptosis by membrane anchoring aie photosensitizer design new prospect for photodynamic cancer Cell Ablation
Elements, 2021Co-Authors: Xingang Liu, Huan Chen, Yukun Duan, Jingjing Liu, Yutong Pan, Bin LiuAbstract:Pyroptosis as a lytic and inflammatory form of Cell death is a powerful tool to fight against cancer. However, pyroptosis is usually activated by chemotherapeutic drugs, which limits its anti-tumor applications due to drug resistance and severe side effects. Herein, we demonstrate that membrane targeting photosensitizers can induce pyroptosis for cancer Cell Ablation with noninvasiveness and low side effects. A series of membrane anchoring photosensitizers (TBD-R PSs) with aggregation-induced emission (AIE) characteristics were prepared through conjugation of TBD and phenyl ring with cationic chains. Upon light irradiation, cytotoxic ROS were produced in situ, resulting in direct membrane damage and superior cancer Cell Ablation. Detailed study revealed that pyroptosis gradually became the dominant Cell death pathway along with the increase of TBD-R PSs membrane anchoring capability. This study offers a photo-activated pyroptosis-based intervention strategy for cancer Cell Ablation.
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photosensitizer bacteria biohybrids promote photodynamic cancer Cell Ablation and intraCellular protein delivery
Chemistry of Materials, 2019Co-Authors: Yukun Duan, Bin LiuAbstract:Live bacteria have drawn widespread interest as carriers to deliver genes and proteins into eukaryotic Cells for the treatment of various cancer types owing to their good biocompatibility and activ...
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simultaneous increase in brightness and singlet oxygen generation of an organic photosensitizer by nanocrystallization
Small, 2018Co-Authors: Purnima Naresh Manghnani, S Ali M Fateminia, Laura Kacenauskaite, Chongjing Zhang, Junsheng Chen, Bo W Laursen, Bin LiuAbstract:Efficient organic photosensitizers are attractive for cancer Cell Ablation in photodynamic therapy. Bright fluorescent photosensitizers are highly desirable for simultaneous imaging and therapy. However, due to fundamental competition between emission and singlet oxygen generation, design attempts to increase singlet oxygen generation almost always leads to the loss of fluorescence. Herein, it is shown for the first time that nanocrystallization enables a simultaneous and significant increase in the brightness and singlet oxygen generation of an organic photosensitizer. Spectroscopic studies show simultaneous enhancement in the visible light absorption and fluorescence after nanocrystallization. The enhanced absorption of visible light in nanocrystals is found to translate directly to the enhanced singlet oxygen production, which shows a higher ability to kill HeLa Cells as compared to their amorphous counterpart.
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a photostable far red near infrared conjugated polymer photosensitizer with aggregation induced emission for image guided cancer Cell Ablation
Macromolecules, 2016Co-Authors: Guangxue Feng, Bin LiuAbstract:Far-red (FR)/near-infrared (NIR) photosensitizer is highly desirable in image-guided photodynamic cancer therapy. Herein, a new conjugated polymer of poly(1,2-bis(4-((6-bromohexyl)oxy)phenyl)-1,2-diphenylethene-co-alt-9,10-anthraquinone) (PTPEAQ) consisting of tetraphenylethylene (TPE), an iconic aggregation-induced emission (AIE) active group as the electron donor, and anthraquinone (AQ) as the acceptor, is prepared for the first time through one-pot Suzuki polymerization. Encapsulation of PTPEAQ with a block copolymer followed by surface functionalization with anti-Her2 affibody yields PTPEAQ-NP-HER2. It shows bright AIE-active FR/NIR emission and efficient singlet oxygen generation under visible light irradiation, which has been successfully used for photodynamic cancer Cell Ablation using SKBR-3 Cells, a type of breast cancer Cell with HER2 overexpression on Cell membrane, as an example.
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dual targeted activatable photosensitizers with aggregation induced emission aie characteristics for image guided photodynamic cancer Cell Ablation
Journal of Materials Chemistry B, 2016Co-Authors: Youyong Yuan, Bin Liu, Chongjing Zhang, Ruoyu ZhangAbstract:The currently available photosensitizers (PSs) for photodynamic therapy (PDT) can easily lead to undesirable normal Cell death due to their intrinsic photo-toxicity and lack of selectivity for cancer Cells. Activatable PSs with high therapeutic efficiency towards cancer Cells but minimized side effects on normal Cells are thus highly desirable. In this work, we developed a probe with dual-targeted activatable PSs that can recognize and ablate cancer Cells with high selectivity. The probe is composed of a fluorophore with aggregation-induced emission (AIE) characteristics which can be used as an imaging agent as well as a PS, a quencher moiety that can be cleaved upon encountering biothiols, and a cyclic arginine–glycine–aspartic acid (cRGD) tripeptide for targeting cancer Cells with overexpressed αvβ3 integrin. The probe itself is non-fluorescent and its ability to generate reactive oxygen species (ROS) is prohibited. However, it could be selectively activated to offer specific fluorescence turn-on with efficient ROS generation in the aggregated state, which was used to ablate cancer Cells overexpressing both αvβ3 integrin receptors and glutathione. As compared to conventional activatable PSs which show quenched fluorescence and reduced ROS generation in the aggregated state, the dual-selection process with enhanced fluorescence and efficient ROS generation of the activated AIE probe in aggregated state offers a high signal-to-background ratio for MDA-MB-231 cancer Cell imaging and Ablation. This strategy thus opens up new opportunities for designing activatable PSs with high selectivity and low intrinsic photo-toxicity for photodynamic cancer Cell Ablation.
Kenji Kohno - One of the best experts on this subject based on the ideXlab platform.
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conversion of adult pancreatic α Cells to β Cells after extreme β Cell loss
Nature, 2010Co-Authors: Fabrizio Thorel, Virginie Nepote, Isabelle Avril, Renaud Desgraz, Simona Chera, Kenji Kohno, Pedro Luis HerreraAbstract:Pancreatic insulin-producing β-Cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, β-Cell loss). It is not known whether adult mammals can differentiate (regenerate) new β-Cells after extreme, total β-Cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-β-Cell) source. Here we show β-Cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-total β-Cell Ablation. If given insulin, the mice survived and showed β-Cell mass augmentation with time. Lineage-tracing to label the glucagon-producing α-Cells before β-Cell Ablation tracked large fractions of regenerated β-Cells as deriving from α-Cells, revealing a previously disregarded degree of pancreatic Cell plasticity. Such inter-endocrine spontaneous adult Cell conversion could be harnessed towards methods of producing β-Cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration. The insulin-producing β-Cells of the pancreas are long lived and replicate little during a lifetime, but can duplicate upon injury or metabolic demand. Work in a transgenic mouse model in which β-Cells are nearly almost completely ablated shows that adult α-Cells, normally responsible for producing the peptide hormone glucagon, can be spontaneously reprogrammed to become β-Cells. This unexpected display of pancreatic Cell plasticity suggests possible diabetes therapies involving either differentiation settings for in vitro Cell production or induced regeneration in vivo. And the production of new models for selective and total Cell killing could reveal previously unrecognized Cell plasticity in other organs. In the pancreas, insulin-producing β-Cells are long-lived and generally replicate seldom. They can do so, however, after increased metabolic demand or after injury. Here, a new transgenic model is developed in which β-Cells are nearly completely ablated in mice. If given insulin, these mice survive, and grow new β-Cells. Lineage-tracing shows that these new β-Cells come from α-Cells, revealing a previously disregarded degree of pancreatic Cell plasticity.
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conversion of adult pancreatic alpha Cells to beta Cells after extreme beta Cell loss
Nature, 2010Co-Authors: Fabrizio Thorel, Virginie Nepote, Isabelle Avril, Renaud Desgraz, Simona Chera, Kenji Kohno, Pedro Luis HerreraAbstract:Pancreatic insulin-producing beta-Cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, beta-Cell loss). It is not known whether adult mammals can differentiate (regenerate) new beta-Cells after extreme, total beta-Cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-beta-Cell) source. Here we show beta-Cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-total beta-Cell Ablation. If given insulin, the mice survived and showed beta-Cell mass augmentation with time. Lineage-tracing to label the glucagon-producing alpha-Cells before beta-Cell Ablation tracked large fractions of regenerated beta-Cells as deriving from alpha-Cells, revealing a previously disregarded degree of pancreatic Cell plasticity. Such inter-endocrine spontaneous adult Cell conversion could be harnessed towards methods of producing beta-Cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration.
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conversion of adult pancreatic α Cells to β Cells after extreme β Cell loss
Nature, 2010Co-Authors: Fabrizio Thorel, Virginie Nepote, Isabelle Avril, Renaud Desgraz, Simona Chera, Kenji Kohno, Pedro Luis HerreraAbstract:Pancreatic insulin-producing beta-Cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, beta-Cell loss). It is not known whether adult mammals can differentiate (regenerate) new beta-Cells after extreme, total beta-Cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-beta-Cell) source. Here we show beta-Cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-total beta-Cell Ablation. If given insulin, the mice survived and showed beta-Cell mass augmentation with time. Lineage-tracing to label the glucagon-producing alpha-Cells before beta-Cell Ablation tracked large fractions of regenerated beta-Cells as deriving from alpha-Cells, revealing a previously disregarded degree of pancreatic Cell plasticity. Such inter-endocrine spontaneous adult Cell conversion could be harnessed towards methods of producing beta-Cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration.
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conversion of adult pancreatic a Cells to b Cells after extreme b Cell loss
2010Co-Authors: Fabrizio Thorel, Isabelle Avril, Renaud Desgraz, Simona Chera, Kenji Kohno, Pedro Luis HerreraAbstract:Pancreaticinsulin-producingb-Cellshavealonglifespan,suchthatinhealthyconditionstheyreplicatelittleduringalifetime. Nevertheless,theyshowincreasedself-duplicationafterincreasedmetabolicdemandorafterinjury(thatis,b-Cellloss).Itis not known whether adult mammals can differentiate (regenerate) new b-Cells after extreme, total b-Cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-b-Cell) source. Here we show b-Cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-totalb-Cell Ablation. If given insulin, the mice survived and showed b-Cell mass augmentation with time. Lineage-tracing to label the glucagon-producing a-Cells before b-Cell Ablation tracked large fractions of regenerated b-Cells as deriving from a-Cells, revealing a previously disregarded degree of pancreatic Cell plasticity. Such inter-endocrine spontaneous adult Cell conversion could be harnessed towards methods of producing b-Cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration.
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diphtheria toxin receptor mediated conditional and targeted Cell Ablation in transgenic mice
Nature Biotechnology, 2001Co-Authors: Michiko Saito, Takao Iwawaki, Choji Taya, Hiromichi Yonekawa, Munehiro Noda, Yoshiaki Inui, Eisuke Mekada, Yukio Kimata, Akio Tsuru, Kenji KohnoAbstract:Specific Cell Ablation is a useful method for analyzing the in vivo function of Cells. We have developed a simple and sensitive method for conditional Cell Ablation in transgenic mice, called "toxin receptor-mediated Cell knockout." We expressed the diphtheria toxin (DT) receptor in transgenic mice using a hepatocyte-specific promoter and found that injection of DT caused fulminant hepatitis. Three independently established transgenic lines demonstrated a good correlation between the sensitivity of hepatocytes to DT and the expression level of the DT receptors. Moreover, the degree of hepatocyte damage was easily controlled over a wide range of doses of injected DT without any obvious abnormalities in other Cells or tissues. This system is useful for generating mouse models of disease and for studying the recovery or regeneration of tissues from Cell damage or loss. As DT is a potent inhibitor of protein synthesis in both growing and non-growing Cells, the method is applicable to a wide range of Cells and tissues in mice or in other DT-insensitive animals.
Ari Waisman - One of the best experts on this subject based on the ideXlab platform.
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A Cre-inducible diphtheria toxin receptor mediates Cell lineage Ablation after toxin administration
Nature Methods, 2005Co-Authors: Thorsten Buch, Steffen Jung, Frank L Heppner, Christine Tertilt, Tobias J A J Heinen, Marcel Kremer, F Thomas Wunderlich, Ari WaismanAbstract:A new system for lineage Ablation is based on transgenic expression of a diphtheria toxin receptor (DTR) in mouse Cells and application of diphtheria toxin (DT). To streamline this approach, we generated Cre-inducible DTR transgenic mice (iDTR) in which Cre-mediated excision of a STOP cassette renders Cells sensitive to DT. We tested the iDTR strain by crossing to the T Cell– and B Cell–specific CD4-Cre and CD19-Cre strains, respectively, and observed efficient Ablation of T and B Cells after exposure to DT. In MOGi-Cre/iDTR double transgenic mice expressing Cre recombinase in oligodendrocytes, we observed myelin loss after intraperitoneal DT injections. Thus, DT crosses the blood-brain barrier and promotes Cell Ablation in the central nervous system. Notably, we show that the developing DT-specific antibody response is weak and not neutralizing, and thus does not impede the efficacy of DT. Our results validate the use of iDTR mice as a tool for Cell Ablation in vivo .
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a cre inducible diphtheria toxin receptor mediates Cell lineage Ablation after toxin administration
Nature Methods, 2005Co-Authors: Thorsten Buch, Steffen Jung, Frank L Heppner, Christine Tertilt, Tobias J A J Heinen, Marcel Kremer, Ari Waisman, Thomas F WunderlichAbstract:A new system for lineage Ablation is based on transgenic expression of a diphtheria toxin receptor (DTR) in mouse Cells and application of diphtheria toxin (DT). To streamline this approach, we generated Cre-inducible DTR transgenic mice (iDTR) in which Cre-mediated excision of a STOP cassette renders Cells sensitive to DT. We tested the iDTR strain by crossing to the T Cell– and B Cell–specific CD4-Cre and CD19-Cre strains, respectively, and observed efficient Ablation of T and B Cells after exposure to DT. In MOGi-Cre/iDTR double transgenic mice expressing Cre recombinase in oligodendrocytes, we observed myelin loss after intraperitoneal DT injections. Thus, DT crosses the blood-brain barrier and promotes Cell Ablation in the central nervous system. Notably, we show that the developing DT-specific antibody response is weak and not neutralizing, and thus does not impede the efficacy of DT. Our results validate the use of iDTR mice as a tool for Cell Ablation in vivo. Constitutive and conditional lineage Ablation allows the investigation of Cell function in the context of the whole organism. To accomplish constitutive Ablation of Cell lineages, several methods have been established. In some of these, progenitors of the investigated Cell type are removed physically 1,2 . Others are based
Stefan Offermanns - One of the best experts on this subject based on the ideXlab platform.
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adhesion receptor adgrg2 gpr64 is in the gi tract selectively expressed in mature intestinal tuft Cells
Molecular metabolism, 2021Co-Authors: Kaare V. Grunddal, Sarah Tonack, Kristoffer L. Egerod, Jonathan James Thompson, Natalia Petersen, Maja S. Engelstoft, Constance Vagne, Céline Keime, Gérard Gradwohl, Stefan OffermannsAbstract:Abstract Objective GPR64/ADGRG2 is an orphan Adhesion G protein-coupled receptor (ADGR) known to be mainly expressed in the parathyroid gland and epididymis. This investigation aimed to delineate the Cellular expression of GPR64 throughout the body with focus on the gastrointestinal (GI) tract. Methods Transgenic Gpr64mCherry reporter mice were histologically examined throughout the body and reporter protein expression in intestinal tuft Cells was confirmed by specific Cell Ablation. The GPCR repertoire of intestinal Gpr64mCherry-positive tuft Cells was analyzed by quantitative RT-PCR analysis and in situ hybridization. The Gpr64mCherry was crossed into the general tuft Cell reporter Trpm5GFP to generate small intestinal organoids for time-lapse imaging. Intestinal tuft Cells were isolated from small intestine, FACS-purified and transcriptionally compared using RNA-seq analysis. Results Expression of the Gpr64mCherry reporter was identified in multiple organs and specifically in olfactory microvillous Cells, enteric nerves, and importantly in respiratory and GI tuft Cells. In the small intestine, Cell Ablation targeting Gpr64-expressing epithelial Cells eliminated tuft Cells. Transcriptional analysis of small intestinal Gpr64mCherry -positive tuft Cells confirmed expression of Gpr64 and the chemo-sensors Sucnr1, Gprc5c, Drd3, and Gpr41/Ffar3. Time-lapse studies of organoids from Trpm5GFP:Gpr64mCherry mice revealed sequential expression of initially Trpm5GFP and subsequently also Gpr64mCherry in maturing intestinal tuft Cells. RNA-seq analysis of small intestinal tuft Cells based on these two markers demonstrated a dynamic change in expression of transcription factors and GPCRs from young to mature tuft Cells. Conclusions GPR64 is expressed in chemosensory epithelial Cells across a broad range of tissues; however, in the GI tract, GPR64 is remarkably selectively expressed in mature versus young immunoregulatory tuft Cells.
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Adhesion receptor ADGRG2/GPR64 is in the GI-tract selectively expressed in mature intestinal tuft Cells
'Elsevier BV', 2021Co-Authors: Kaare V. Grunddal, Sarah Tonack, Kristoffer L. Egerod, Jonathan James Thompson, Natalia Petersen, Maja S. Engelstoft, Constance Vagne, Céline Keime, Gérard Gradwohl, Stefan OffermannsAbstract:Objective: GPR64/ADGRG2 is an orphan Adhesion G protein-coupled receptor (ADGR) known to be mainly expressed in the parathyroid gland and epididymis. This investigation aimed to delineate the Cellular expression of GPR64 throughout the body with focus on the gastrointestinal (GI) tract. Methods: Transgenic Gpr64mCherry reporter mice were histologically examined throughout the body and reporter protein expression in intestinal tuft Cells was confirmed by specific Cell Ablation. The GPCR repertoire of intestinal Gpr64mCherry-positive tuft Cells was analyzed by quantitative RT-PCR analysis and in situ hybridization. The Gpr64mCherry was crossed into the general tuft Cell reporter Trpm5GFP to generate small intestinal organoids for time-lapse imaging. Intestinal tuft Cells were isolated from small intestine, FACS-purified and transcriptionally compared using RNA-seq analysis. Results: Expression of the Gpr64mCherry reporter was identified in multiple organs and specifically in olfactory microvillous Cells, enteric nerves, and importantly in respiratory and GI tuft Cells. In the small intestine, Cell Ablation targeting Gpr64-expressing epithelial Cells eliminated tuft Cells. Transcriptional analysis of small intestinal Gpr64mCherry -positive tuft Cells confirmed expression of Gpr64 and the chemo-sensors Sucnr1, Gprc5c, Drd3, and Gpr41/Ffar3. Time-lapse studies of organoids from Trpm5GFP:Gpr64mCherry mice revealed sequential expression of initially Trpm5GFP and subsequently also Gpr64mCherry in maturing intestinal tuft Cells. RNA-seq analysis of small intestinal tuft Cells based on these two markers demonstrated a dynamic change in expression of transcription factors and GPCRs from young to mature tuft Cells. Conclusions: GPR64 is expressed in chemosensory epithelial Cells across a broad range of tissues; however, in the GI tract, GPR64 is remarkably selectively expressed in mature versus young immunoregulatory tuft Cells
Pedro Luis Herrera - One of the best experts on this subject based on the ideXlab platform.
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conversion of adult pancreatic α Cells to β Cells after extreme β Cell loss
Nature, 2010Co-Authors: Fabrizio Thorel, Virginie Nepote, Isabelle Avril, Renaud Desgraz, Simona Chera, Kenji Kohno, Pedro Luis HerreraAbstract:Pancreatic insulin-producing β-Cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, β-Cell loss). It is not known whether adult mammals can differentiate (regenerate) new β-Cells after extreme, total β-Cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-β-Cell) source. Here we show β-Cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-total β-Cell Ablation. If given insulin, the mice survived and showed β-Cell mass augmentation with time. Lineage-tracing to label the glucagon-producing α-Cells before β-Cell Ablation tracked large fractions of regenerated β-Cells as deriving from α-Cells, revealing a previously disregarded degree of pancreatic Cell plasticity. Such inter-endocrine spontaneous adult Cell conversion could be harnessed towards methods of producing β-Cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration. The insulin-producing β-Cells of the pancreas are long lived and replicate little during a lifetime, but can duplicate upon injury or metabolic demand. Work in a transgenic mouse model in which β-Cells are nearly almost completely ablated shows that adult α-Cells, normally responsible for producing the peptide hormone glucagon, can be spontaneously reprogrammed to become β-Cells. This unexpected display of pancreatic Cell plasticity suggests possible diabetes therapies involving either differentiation settings for in vitro Cell production or induced regeneration in vivo. And the production of new models for selective and total Cell killing could reveal previously unrecognized Cell plasticity in other organs. In the pancreas, insulin-producing β-Cells are long-lived and generally replicate seldom. They can do so, however, after increased metabolic demand or after injury. Here, a new transgenic model is developed in which β-Cells are nearly completely ablated in mice. If given insulin, these mice survive, and grow new β-Cells. Lineage-tracing shows that these new β-Cells come from α-Cells, revealing a previously disregarded degree of pancreatic Cell plasticity.
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conversion of adult pancreatic alpha Cells to beta Cells after extreme beta Cell loss
Nature, 2010Co-Authors: Fabrizio Thorel, Virginie Nepote, Isabelle Avril, Renaud Desgraz, Simona Chera, Kenji Kohno, Pedro Luis HerreraAbstract:Pancreatic insulin-producing beta-Cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, beta-Cell loss). It is not known whether adult mammals can differentiate (regenerate) new beta-Cells after extreme, total beta-Cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-beta-Cell) source. Here we show beta-Cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-total beta-Cell Ablation. If given insulin, the mice survived and showed beta-Cell mass augmentation with time. Lineage-tracing to label the glucagon-producing alpha-Cells before beta-Cell Ablation tracked large fractions of regenerated beta-Cells as deriving from alpha-Cells, revealing a previously disregarded degree of pancreatic Cell plasticity. Such inter-endocrine spontaneous adult Cell conversion could be harnessed towards methods of producing beta-Cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration.
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conversion of adult pancreatic α Cells to β Cells after extreme β Cell loss
Nature, 2010Co-Authors: Fabrizio Thorel, Virginie Nepote, Isabelle Avril, Renaud Desgraz, Simona Chera, Kenji Kohno, Pedro Luis HerreraAbstract:Pancreatic insulin-producing beta-Cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, beta-Cell loss). It is not known whether adult mammals can differentiate (regenerate) new beta-Cells after extreme, total beta-Cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-beta-Cell) source. Here we show beta-Cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-total beta-Cell Ablation. If given insulin, the mice survived and showed beta-Cell mass augmentation with time. Lineage-tracing to label the glucagon-producing alpha-Cells before beta-Cell Ablation tracked large fractions of regenerated beta-Cells as deriving from alpha-Cells, revealing a previously disregarded degree of pancreatic Cell plasticity. Such inter-endocrine spontaneous adult Cell conversion could be harnessed towards methods of producing beta-Cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration.
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conversion of adult pancreatic a Cells to b Cells after extreme b Cell loss
2010Co-Authors: Fabrizio Thorel, Isabelle Avril, Renaud Desgraz, Simona Chera, Kenji Kohno, Pedro Luis HerreraAbstract:Pancreaticinsulin-producingb-Cellshavealonglifespan,suchthatinhealthyconditionstheyreplicatelittleduringalifetime. Nevertheless,theyshowincreasedself-duplicationafterincreasedmetabolicdemandorafterinjury(thatis,b-Cellloss).Itis not known whether adult mammals can differentiate (regenerate) new b-Cells after extreme, total b-Cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-b-Cell) source. Here we show b-Cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-totalb-Cell Ablation. If given insulin, the mice survived and showed b-Cell mass augmentation with time. Lineage-tracing to label the glucagon-producing a-Cells before b-Cell Ablation tracked large fractions of regenerated b-Cells as deriving from a-Cells, revealing a previously disregarded degree of pancreatic Cell plasticity. Such inter-endocrine spontaneous adult Cell conversion could be harnessed towards methods of producing b-Cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration.