The Experts below are selected from a list of 6522 Experts worldwide ranked by ideXlab platform
Paul Guilhamon - One of the best experts on this subject based on the ideXlab platform.
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Fate Mapping of human glioblastoma reveals an invariant stem cell hierarchy
Nature, 2017Co-Authors: Xiaoyang Lan, David J Jorg, Florence M G Cavalli, Laura M Richards, Long V Nguyen, Robert Vanner, Paul GuilhamonAbstract:Using unique barcodes for tumour cells, the authors explore the dynamics of human glioblastoma subpopulations, and suggest that clonal heterogeneity emerges through stochastic Fate decisions of a neutral proliferative hierarchy.
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Fate Mapping of human glioblastoma reveals an invariant stem cell hierarchy
Nature, 2017Co-Authors: Xiaoyang Lan, David J Jorg, Florence M G Cavalli, Laura M Richards, Long V Nguyen, Robert Vanner, Paul GuilhamonAbstract:Human glioblastomas harbour a subpopulation of glioblastoma stem cells that drive tumorigenesis. However, the origin of intratumoural functional heterogeneity between glioblastoma cells remains poorly understood. Here we study the clonal evolution of barcoded glioblastoma cells in an unbiased way following serial xenotransplantation to define their individual Fate behaviours. Independent of an evolving mutational signature, we show that the growth of glioblastoma clones in vivo is consistent with a remarkably neutral process involving a conserved proliferative hierarchy rooted in glioblastoma stem cells. In this model, slow-cycling stem-like cells give rise to a more rapidly cycling progenitor population with extensive self-maintenance capacity, which in turn generates non-proliferative cells. We also identify rare 'outlier' clones that deviate from these dynamics, and further show that chemotherapy facilitates the expansion of pre-existing drug-resistant glioblastoma stem cells. Finally, we show that functionally distinct glioblastoma stem cells can be separately targeted using epigenetic compounds, suggesting new avenues for glioblastoma-targeted therapy.
Bin Zhou - One of the best experts on this subject based on the ideXlab platform.
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dual recombinases based genetic lineage tracing for stem cell research with enhanced precision
Science China-life Sciences, 2021Co-Authors: Hengwei Jin, Bin Zhou, Kuo LiuAbstract:Stem cell research has become a hot topic in biology, as the understanding of stem cell biology can provide new insights for both regenerative medicine and clinical treatment of diseases. Accurately deciphering the Fate of stem cells is the basis for understanding the mechanism and function of stem cells during tissue repair and regeneration. Cre-loxP-mediated recombination has been widely applied in Fate Mapping of stem cells for many years. However, nonspecific labeling by conventional cell lineage tracing strategies has led to discrepancies or even controversies in multiple fields. Recently, dual recombinase-mediated lineage tracing strategies have been developed to improve both the resolution and precision of stem cell Fate Mapping. These new genetic strategies also expand the application of lineage tracing in studying cell origin and Fate. Here, we review cell lineage tracing methods, especially dual genetic approaches, and then provide examples to describe how they are used to study stem cell Fate plasticity and function in vivo.
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genetic lineage tracing with multiple dna recombinases a user s guide for conducting more precise cell Fate Mapping studies
Journal of Biological Chemistry, 2020Co-Authors: Bin Zhou, Kuo Liu, Hengwei JinAbstract:Site-specific recombinases, such as Cre, are a widely used tool for genetic lineage tracing in the fields of developmental biology, neural science, stem cell biology, and regenerative medicine. However, nonspecific cell labeling by some genetic Cre tools remains a technical limitation of this recombination system, which has resulted in data misinterpretation and led to many controversies in the scientific community. In the past decade, to enhance the specificity and precision of genetic targeting, researchers have used two or more orthogonal recombinases simultaneously for labeling cell lineages. Here, we review the history of cell-tracing strategies and then elaborate on the working principle and application of a recently developed dual genetic lineage-tracing approach for cell Fate studies. We place an emphasis on discussing the technical strengths and caveats of different methods, with the goal to develop more specific and efficient tracing technologies for cell Fate Mapping. Our review also provides several examples for how to use different types of DNA recombinase–mediated lineage-tracing strategies to improve the resolution of the cell Fate Mapping in order to probe and explore cell Fate–related biological phenomena in the life sciences.
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genetic Fate Mapping defines the vascular potential of endocardial cells in the adult heart
Circulation Research, 2018Co-Authors: Juan Tang, Wenjuan Pu, Xiuzhen Huang, Lingjuan He, Libo Zhang, Yan Li, Hui Zhang, Bin ZhouAbstract:Rationale: Endocardium is the major source of coronary endothelial cells (ECs) in the fetal and neonatal hearts. It remains unclear whether endocardium in the adult stage is also the main origin of neovascularization after cardiac injury. Objective: To define the vascular potential of adult endocardium in homeostasis and after cardiac injuries by Fate-Mapping studies. Methods and Results: We generate an inducible adult endocardial Cre line ( Npr3 [natriuretic peptide receptor C]- CreER ) and show that Npr3-CreER efficiently and specifically labels endocardial cells but not coronary blood vessels in the adult heart. The adult endocardial cells do not contribute to any vascular ECs during cardiac homeostasis. To examine the formation of blood vessels from endocardium after injury, we generate 4 cardiac injury models with Npr3-CreER mice: myocardial infarction, myocardial ischemia–reperfusion, cryoinjury, and transverse aortic constriction. Lineage tracing experiments show that adult endocardium minimally contributes to coronary ECs after myocardial infarction. In the myocardial ischemia–reperfusion, cryoinjury, or transverse aortic constriction models, adult endocardial cells do not give rise to any vascular ECs, and they remain on the inner surface of myocardium that connects with lumen circulation. In the myocardial infarction model, very few endocardial cells are trapped in the infarct zone of myocardium shortly after ligation of coronary artery, indicating the involvement of endocardial entrapment during blood vessels formation. When these adult endocardial cells are relocated and trapped in the infarcted myocardium by transplantation or myocardial constriction model, very few endocardial cells survive and gain vascular EC properties, and their contribution to neovascularization in the injured myocardium remains minimal. Conclusions: Unlike its fetal or neonatal counterpart, adult endocardium naturally generates minimal, if any, coronary arteries or vascular ECs during cardiac homeostasis or after injuries.
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Reassessment of Isl1 and Nkx2-5 cardiac Fate maps using a Gata4-based reporter of Cre activity.
Developmental Biology, 2008Co-Authors: Bin ZhouAbstract:Isl1 and Nkx2-5-expressing cardiovascular progenitors play pivotal roles in cardiogenesis. Previously reported Cre-based Fate-Mapping studies showed that Isl1 progenitors contribute predominantly to the derivatives of the second heart field, and Nkx2-5 progenitors contributed mainly to the cardiomyocyte lineage. However, partial recombination of Cre reporter genes can complicate interpretation of Cre Fate-Mapping experiments. We found that a Gata4-based Cre-activated reporter was recombined by Isl1(Cre) and Nkx2-5(Cre) in a substantially broader domain than previously reported using standard Cre-activated reporters. The expanded Isl1 and Nkx2-5 cardiac Fate maps were remarkably similar, and included extensive contributions to cardiomyocyte, endocardial, and smooth muscle lineages in all four cardiac chambers. These data indicate that Isl1 is expressed in progenitors of both primary and secondary heart fields, and that Nkx2-5 is expressed in progenitors of cardiac endothelium and smooth muscle, in addition to cardiomyocytes. These results have important implications for our understanding of cardiac lineage diversification in vivo, and for the interpretation of Cre-based Fate maps.
M Ole D Isacson - One of the best experts on this subject based on the ideXlab platform.
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Fate Mapping and lineage analyses demonstrate the production of a large number of striatal neuroblasts after transforming growth factor α and noggin striatal infusions into the dopamine depleted striatum
Stem Cells, 2008Co-Authors: Antoine De Chevigny, Oliver Cooper, Angel Vinuela, Casper Reskenielsen, Diane C Lagace, Amelia J Eisch, M Ole D IsacsonAbstract:Infusion of transforming growth factor α (TGFα) into the adult dopamine (DA)-depleted striatum generates a local population of nestin+/proliferating cell nuclear antigen (PCNA)+ newborn cells. The precise origin and Fate of these new striatal cells are unknown, making it difficult to direct them for neural repair in Parkinson's disease. Experiments in rats using 5-bromo-2′-deoxyuridine (BrdU) to label neural progenitor cells showed that during TGFα infusion in the DA-depleted striatum, newborn striatal cells formed a homogeneous population of precursors, with the majority coexpressing nestin, Mash1, Olig2, and epidermal growth factor receptor, consistent with the phenotype of multipotent C cells. Upon TGFα pump withdrawal, the subventricular zone (SVZ) was repopulated by neuroblasts. Strikingly, during this period, numerous clusters of doublecortin+/polysialylated neuronal cell adhesion molecule+ neuroblasts were also produced in the ipsilateral medial striatum. In parallel, striatal BrdU+/glial fibrillary acidic protein+ astrocytes were generated, but no BrdU+/O4+/CNPase+ oligodendrocytes were generated. Infusion of the neuralizing bone morphogenetic protein antagonist noggin after TGFα pump withdrawal increased the neuroblast-to-astrocyte ratio among new striatal cells by blocking glial differentiation but did not alter striatal neurogenesis. At no time or treatment condition were differentiated neurons generated, including DA neurons. Using 6-hydroxydopamine-lesioned nestin-CreERT2/R26R-YFP mice that allow genetic Fate-Mapping of SVZ nestin+ cells, we show that TGFα-generated striatal cells originate from SVZ nestin+ precursors that confirmed data from the rats on the phenotype and Fate of striatal nestin+/PCNA+ cells upon TGFα withdrawal. This work demonstrates that a large population of multipotent striatal C-like cells can be generated in the DA-depleted striatum that do not spontaneously differentiate into DA neurons. Disclosure of potential conflicts of interest is found at the end of this article.
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Fate Mapping and lineage analyses demonstrate the production of a large number of striatal neuroblasts after transforming growth factor α and noggin striatal infusions into the dopamine depleted striatum
Stem Cells, 2008Co-Authors: Antoine De Chevigny, Oliver Cooper, Angel Vinuela, Casper Reskenielsen, Diane C Lagace, Amelia J Eisch, M Ole D IsacsonAbstract:Infusion of transforming growth factor alpha (TGFalpha) into the adult dopamine (DA)-depleted striatum generates a local population of nestin(+)/proliferating cell nuclear antigen (PCNA)(+) newborn cells. The precise origin and Fate of these new striatal cells are unknown, making it difficult to direct them for neural repair in Parkinson's disease. Experiments in rats using 5-bromo-2'-deoxyuridine (BrdU) to label neural progenitor cells showed that during TGFalpha infusion in the DA-depleted striatum, newborn striatal cells formed a homogeneous population of precursors, with the majority coexpressing nestin, Mash1, Olig2, and epidermal growth factor receptor, consistent with the phenotype of multipotent C cells. Upon TGFalpha pump withdrawal, the subventricular zone (SVZ) was repopulated by neuroblasts. Strikingly, during this period, numerous clusters of doublecortin(+)/polysialylated neuronal cell adhesion molecule(+) neuroblasts were also produced in the ipsilateral medial striatum. In parallel, striatal BrdU(+)/glial fibrillary acidic protein(+) astrocytes were generated, but no BrdU(+)/O4(+)/CNPase(+) oligodendrocytes were generated. Infusion of the neuralizing bone morphogenetic protein antagonist noggin after TGFalpha pump withdrawal increased the neuroblast-to-astrocyte ratio among new striatal cells by blocking glial differentiation but did not alter striatal neurogenesis. At no time or treatment condition were differentiated neurons generated, including DA neurons. Using 6-hydroxydopamine-lesioned nestin-CreER(T2)/R26R-YFP mice that allow genetic Fate-Mapping of SVZ nestin(+) cells, we show that TGFalpha-generated striatal cells originate from SVZ nestin(+) precursors that confirmed data from the rats on the phenotype and Fate of striatal nestin(+)/PCNA(+) cells upon TGFalpha withdrawal. This work demonstrates that a large population of multipotent striatal C-like cells can be generated in the DA-depleted striatum that do not spontaneously differentiate into DA neurons.
Frederic Geissmann - One of the best experts on this subject based on the ideXlab platform.
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the origin of tissue resident macrophages when an erythro myeloid progenitor is an erythro myeloid progenitor
Immunity, 2015Co-Authors: Frederic Geissmann, Katrin Busch, Hans Reimer Rodewald, Elisa Gomez Perdiguero, Kay Klapproth, Christian Schulz, Marella F T R De BruijnAbstract:Sheng, Ruedl, and Karjalainen published in Immunity (Sheng et al., 2015) a Fate-Mapping model where the expression of Cre recombinase was inducible in Kit-expressing cells (Kit-MeriCreMer mice). In this system, the authors also revisited the origin of adult tissue-resident macrophages. For a long time, these macrophages have been assumed to be monocyte derivatives and hence ultimately to originate from adult bone marrow stem cells. In recent years, this view has been completely revised by the work of several groups (Schulz et al., 2012; Hashimoto et al., 2013), and in the field there is now a view that resident macrophages in most tissues do not arise from adult hematopoietic stem cells (HSCs) but rather develop at pre-natal stages and persist autonomously in adult tissues (at least under steady-state conditions).
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Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice
Nature Immunology, 2014Co-Authors: Calum C. Bain, Alberto Bravo-blas, Elisa Gomez Perdiguero, Charlotte L. Scott, Frederic Geissmann, Lisa C Osborne, Bernard Malissen, Sandrine Henri, David Artis, Allan Mci. MowatAbstract:The paradigm that macrophages that reside in steady-state tissues are derived from embryonic precursors has never been investigated in the intestine, which contains the largest pool of macrophages. Using Fate-Mapping models and monocytopenic mice, together with bone marrow chimera and parabiotic models, we found that embryonic precursor cells seeded the intestinal mucosa and demonstrated extensive in situ proliferation during the neonatal period. However, these cells did not persist in the intestine of adult mice. Instead, they were replaced around the time of weaning by the chemokine receptor CCR2-dependent influx of Ly6C(hi) monocytes that differentiated locally into mature, anti-inflammatory macrophages. This process was driven largely by the microbiota and had to be continued throughout adult life to maintain a normal intestinal macrophage pool.
Antoine De Chevigny - One of the best experts on this subject based on the ideXlab platform.
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Fate Mapping and lineage analyses demonstrate the production of a large number of striatal neuroblasts after transforming growth factor α and noggin striatal infusions into the dopamine depleted striatum
Stem Cells, 2008Co-Authors: Antoine De Chevigny, Oliver Cooper, Angel Vinuela, Casper Reskenielsen, Diane C Lagace, Amelia J Eisch, M Ole D IsacsonAbstract:Infusion of transforming growth factor α (TGFα) into the adult dopamine (DA)-depleted striatum generates a local population of nestin+/proliferating cell nuclear antigen (PCNA)+ newborn cells. The precise origin and Fate of these new striatal cells are unknown, making it difficult to direct them for neural repair in Parkinson's disease. Experiments in rats using 5-bromo-2′-deoxyuridine (BrdU) to label neural progenitor cells showed that during TGFα infusion in the DA-depleted striatum, newborn striatal cells formed a homogeneous population of precursors, with the majority coexpressing nestin, Mash1, Olig2, and epidermal growth factor receptor, consistent with the phenotype of multipotent C cells. Upon TGFα pump withdrawal, the subventricular zone (SVZ) was repopulated by neuroblasts. Strikingly, during this period, numerous clusters of doublecortin+/polysialylated neuronal cell adhesion molecule+ neuroblasts were also produced in the ipsilateral medial striatum. In parallel, striatal BrdU+/glial fibrillary acidic protein+ astrocytes were generated, but no BrdU+/O4+/CNPase+ oligodendrocytes were generated. Infusion of the neuralizing bone morphogenetic protein antagonist noggin after TGFα pump withdrawal increased the neuroblast-to-astrocyte ratio among new striatal cells by blocking glial differentiation but did not alter striatal neurogenesis. At no time or treatment condition were differentiated neurons generated, including DA neurons. Using 6-hydroxydopamine-lesioned nestin-CreERT2/R26R-YFP mice that allow genetic Fate-Mapping of SVZ nestin+ cells, we show that TGFα-generated striatal cells originate from SVZ nestin+ precursors that confirmed data from the rats on the phenotype and Fate of striatal nestin+/PCNA+ cells upon TGFα withdrawal. This work demonstrates that a large population of multipotent striatal C-like cells can be generated in the DA-depleted striatum that do not spontaneously differentiate into DA neurons. Disclosure of potential conflicts of interest is found at the end of this article.
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Fate Mapping and lineage analyses demonstrate the production of a large number of striatal neuroblasts after transforming growth factor α and noggin striatal infusions into the dopamine depleted striatum
Stem Cells, 2008Co-Authors: Antoine De Chevigny, Oliver Cooper, Angel Vinuela, Casper Reskenielsen, Diane C Lagace, Amelia J Eisch, M Ole D IsacsonAbstract:Infusion of transforming growth factor alpha (TGFalpha) into the adult dopamine (DA)-depleted striatum generates a local population of nestin(+)/proliferating cell nuclear antigen (PCNA)(+) newborn cells. The precise origin and Fate of these new striatal cells are unknown, making it difficult to direct them for neural repair in Parkinson's disease. Experiments in rats using 5-bromo-2'-deoxyuridine (BrdU) to label neural progenitor cells showed that during TGFalpha infusion in the DA-depleted striatum, newborn striatal cells formed a homogeneous population of precursors, with the majority coexpressing nestin, Mash1, Olig2, and epidermal growth factor receptor, consistent with the phenotype of multipotent C cells. Upon TGFalpha pump withdrawal, the subventricular zone (SVZ) was repopulated by neuroblasts. Strikingly, during this period, numerous clusters of doublecortin(+)/polysialylated neuronal cell adhesion molecule(+) neuroblasts were also produced in the ipsilateral medial striatum. In parallel, striatal BrdU(+)/glial fibrillary acidic protein(+) astrocytes were generated, but no BrdU(+)/O4(+)/CNPase(+) oligodendrocytes were generated. Infusion of the neuralizing bone morphogenetic protein antagonist noggin after TGFalpha pump withdrawal increased the neuroblast-to-astrocyte ratio among new striatal cells by blocking glial differentiation but did not alter striatal neurogenesis. At no time or treatment condition were differentiated neurons generated, including DA neurons. Using 6-hydroxydopamine-lesioned nestin-CreER(T2)/R26R-YFP mice that allow genetic Fate-Mapping of SVZ nestin(+) cells, we show that TGFalpha-generated striatal cells originate from SVZ nestin(+) precursors that confirmed data from the rats on the phenotype and Fate of striatal nestin(+)/PCNA(+) cells upon TGFalpha withdrawal. This work demonstrates that a large population of multipotent striatal C-like cells can be generated in the DA-depleted striatum that do not spontaneously differentiate into DA neurons.
