The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Travis W Bainbridge - One of the best experts on this subject based on the ideXlab platform.
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targeting ptprk rspo3 colon tumours promotes differentiation and loss of Stem Cell function
Nature, 2016Co-Authors: Elaine E Storm, Felipe De Sousa E Melo, Noelyn M Kljavin, Steffen Durinck, Jarrod Tremayne, Christine Tan, Cecilia Chiu, Thinh S Pham, Jo Anne Hongo, Travis W BainbridgeAbstract:Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed. We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours. Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the Stem-Cell Compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a Stem-Cell Compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of Stem-Cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.
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targeting ptprk rspo3 colon tumours promotes differentiation and loss of Stem Cell function
Nature, 2016Co-Authors: Elaine E Storm, Felipe De Sousa E Melo, Noelyn M Kljavin, Steffen Durinck, Jarrod Tremayne, Cecilia Chiu, Thinh S Pham, Jo Anne Hongo, Xiaofen Ye, Travis W BainbridgeAbstract:Antibody-mediated inhibition of R-spondin-3 in colorectal tumours decreases tumour growth and promotes differentiation—these effects are associated with a decrease in expression of genes associated with Stem-Cell function. Frederic de Sauvage and colleagues have previously identified translocations in genes encoding the Wnt regulator R-spondins in some colorectal tumours. Here they demonstrate that antibody-mediated inhibition of R-spondin 3 (RSPO3) in such tumours decreases tumour growth and promotes differentiation. These effects are associated with a decrease in expression of genes associated with Stem Cell function. This work raises the possibility of targeting Stem -Cell properties within tumours as therapeutic approach in colorectal tumours. Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed1,2,3. We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours4. Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the Stem-Cell Compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a Stem-Cell Compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of Stem-Cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.
Hans B Sieburg - One of the best experts on this subject based on the ideXlab platform.
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clonal diversity of the Stem Cell Compartment
Current Opinion in Hematology, 2006Co-Authors: Christa E Mullersieburg, Hans B SieburgAbstract:Purpose of review Hematopoietic Stem Cells are functionally heterogeneous even when isolated as phenotypically homogenous populations. How this heterogeneity is generated is incompletely understood. Several models have been formulated to explain the generation of diversity. All of these assume the existence of a single type of hematopoietic Stem Cell that generates heterogeneous daughter Stem Cells in response to extrinsic or intrinsic (stochastic) signals. This view has encouraged the idea that Stem Cells can be instructed to adapt their function. Newer data, however, challenge this concept. Here, we summarize these findings and discuss their implication for applications of Stem Cells. Recent findings Hematopoietic Stem Cells that differ in function have been documented during development and within the adult Stem Cell Compartment. The differences in function are stably inherited to daughter Stem Cells when these Cells proliferate to self-renew. Collectively, the data show that the adult Stem Cell Compartment consists of a limited number of distinct classes of Stem Cells. Summary The most important Stem Cell functions, including self-renewal and differentiation capacity, are preprogrammed through epigenetic or genetic mechanisms. Thus, Stem Cells are much more predictable than previously thought. Changes in the Stem Cell Compartment through disease or aging can be interpreted as shifts in its clonal composition, rather than a modification of individual hematopoietic Stem Cells.
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the god of hematopoietic Stem Cells a clonal diversity model of the Stem Cell Compartment
Cell Cycle, 2006Co-Authors: Christa E Mullersieburg, Hans B SieburgAbstract:Hematopoietic Stem Cells (HSC) show heterogeneous behavior even when isolated as phenotypically homogeneous populations. The Cellular and molecular mechanisms that control the generation of diversity (GOD) in the HSC Compartment are not well understood, but have been the focus of much debate. There is increasing evidence that the most important HSC functions, self-renewal and differentiation, are epigenetically preprogrammed and therefore predictable. Indeed, recent data show that the adult HSC Compartment consists of a limited number of functionally distinct subsets of HSC. This contradicts older models of HSC behavior, which postulated a single type of HSC that can be continuously molded into different subtypes of HSC. We propose a clonal diversity model where the adult HSC Compartment consists of a fixed number of different types of HSC, each with epigenetically preprogrammed behavior. Aging or disease may change the overall function of the HSC population. The model predicts that these changes reflect the relative composition of the HSC subsets, rather than changes in individual HSC. This view has implications for using HSC in experimental and clinical settings. Selection for the appropriate subsets of HSC, rather than attempts to force HSC to adjust, should improve their utility in transplantation and gene transfer applications.
Elaine E Storm - One of the best experts on this subject based on the ideXlab platform.
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targeting ptprk rspo3 colon tumours promotes differentiation and loss of Stem Cell function
Nature, 2016Co-Authors: Elaine E Storm, Felipe De Sousa E Melo, Noelyn M Kljavin, Steffen Durinck, Jarrod Tremayne, Christine Tan, Cecilia Chiu, Thinh S Pham, Jo Anne Hongo, Travis W BainbridgeAbstract:Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed. We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours. Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the Stem-Cell Compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a Stem-Cell Compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of Stem-Cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.
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targeting ptprk rspo3 colon tumours promotes differentiation and loss of Stem Cell function
Nature, 2016Co-Authors: Elaine E Storm, Felipe De Sousa E Melo, Noelyn M Kljavin, Steffen Durinck, Jarrod Tremayne, Cecilia Chiu, Thinh S Pham, Jo Anne Hongo, Xiaofen Ye, Travis W BainbridgeAbstract:Antibody-mediated inhibition of R-spondin-3 in colorectal tumours decreases tumour growth and promotes differentiation—these effects are associated with a decrease in expression of genes associated with Stem-Cell function. Frederic de Sauvage and colleagues have previously identified translocations in genes encoding the Wnt regulator R-spondins in some colorectal tumours. Here they demonstrate that antibody-mediated inhibition of R-spondin 3 (RSPO3) in such tumours decreases tumour growth and promotes differentiation. These effects are associated with a decrease in expression of genes associated with Stem Cell function. This work raises the possibility of targeting Stem -Cell properties within tumours as therapeutic approach in colorectal tumours. Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed1,2,3. We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours4. Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the Stem-Cell Compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a Stem-Cell Compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of Stem-Cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.
Felipe De Sousa E Melo - One of the best experts on this subject based on the ideXlab platform.
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Stem Cell plasticity enables hair regeneration following lgr5 Cell loss
Nature Cell Biology, 2017Co-Authors: Joerg D Hoeck, Brian Biehs, Antonina V Kurtova, Felipe De Sousa E Melo, Noelyn M Kljavin, Hartmut Koeppen, Bruno Alicke, Zora Modrusan, Robert Piskol, Frederic J De SauvageAbstract:Hoeck et al. show that disruption of the hair follicle Stem Cell Compartment by loss of Lgr5+ Stem Cells is followed by an inflammatory response and CD34+ Stem Cell activation and proliferation, to eventually replenish the Lgr5+ population.
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targeting ptprk rspo3 colon tumours promotes differentiation and loss of Stem Cell function
Nature, 2016Co-Authors: Elaine E Storm, Felipe De Sousa E Melo, Noelyn M Kljavin, Steffen Durinck, Jarrod Tremayne, Christine Tan, Cecilia Chiu, Thinh S Pham, Jo Anne Hongo, Travis W BainbridgeAbstract:Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed. We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours. Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the Stem-Cell Compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a Stem-Cell Compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of Stem-Cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.
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targeting ptprk rspo3 colon tumours promotes differentiation and loss of Stem Cell function
Nature, 2016Co-Authors: Elaine E Storm, Felipe De Sousa E Melo, Noelyn M Kljavin, Steffen Durinck, Jarrod Tremayne, Cecilia Chiu, Thinh S Pham, Jo Anne Hongo, Xiaofen Ye, Travis W BainbridgeAbstract:Antibody-mediated inhibition of R-spondin-3 in colorectal tumours decreases tumour growth and promotes differentiation—these effects are associated with a decrease in expression of genes associated with Stem-Cell function. Frederic de Sauvage and colleagues have previously identified translocations in genes encoding the Wnt regulator R-spondins in some colorectal tumours. Here they demonstrate that antibody-mediated inhibition of R-spondin 3 (RSPO3) in such tumours decreases tumour growth and promotes differentiation. These effects are associated with a decrease in expression of genes associated with Stem Cell function. This work raises the possibility of targeting Stem -Cell properties within tumours as therapeutic approach in colorectal tumours. Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed1,2,3. We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours4. Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the Stem-Cell Compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a Stem-Cell Compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of Stem-Cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.
Noelyn M Kljavin - One of the best experts on this subject based on the ideXlab platform.
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Stem Cell plasticity enables hair regeneration following lgr5 Cell loss
Nature Cell Biology, 2017Co-Authors: Joerg D Hoeck, Brian Biehs, Antonina V Kurtova, Felipe De Sousa E Melo, Noelyn M Kljavin, Hartmut Koeppen, Bruno Alicke, Zora Modrusan, Robert Piskol, Frederic J De SauvageAbstract:Hoeck et al. show that disruption of the hair follicle Stem Cell Compartment by loss of Lgr5+ Stem Cells is followed by an inflammatory response and CD34+ Stem Cell activation and proliferation, to eventually replenish the Lgr5+ population.
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targeting ptprk rspo3 colon tumours promotes differentiation and loss of Stem Cell function
Nature, 2016Co-Authors: Elaine E Storm, Felipe De Sousa E Melo, Noelyn M Kljavin, Steffen Durinck, Jarrod Tremayne, Christine Tan, Cecilia Chiu, Thinh S Pham, Jo Anne Hongo, Travis W BainbridgeAbstract:Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed. We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours. Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the Stem-Cell Compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a Stem-Cell Compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of Stem-Cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.
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targeting ptprk rspo3 colon tumours promotes differentiation and loss of Stem Cell function
Nature, 2016Co-Authors: Elaine E Storm, Felipe De Sousa E Melo, Noelyn M Kljavin, Steffen Durinck, Jarrod Tremayne, Cecilia Chiu, Thinh S Pham, Jo Anne Hongo, Xiaofen Ye, Travis W BainbridgeAbstract:Antibody-mediated inhibition of R-spondin-3 in colorectal tumours decreases tumour growth and promotes differentiation—these effects are associated with a decrease in expression of genes associated with Stem-Cell function. Frederic de Sauvage and colleagues have previously identified translocations in genes encoding the Wnt regulator R-spondins in some colorectal tumours. Here they demonstrate that antibody-mediated inhibition of R-spondin 3 (RSPO3) in such tumours decreases tumour growth and promotes differentiation. These effects are associated with a decrease in expression of genes associated with Stem Cell function. This work raises the possibility of targeting Stem -Cell properties within tumours as therapeutic approach in colorectal tumours. Colorectal cancer remains a major unmet medical need, prompting large-scale genomics efforts in the field to identify molecular drivers for which targeted therapies might be developed1,2,3. We previously reported the identification of recurrent translocations in R-spondin genes present in a subset of colorectal tumours4. Here we show that targeting RSPO3 in PTPRK-RSPO3-fusion-positive human tumour xenografts inhibits tumour growth and promotes differentiation. Notably, genes expressed in the Stem-Cell Compartment of the intestine were among those most sensitive to anti-RSPO3 treatment. This observation, combined with functional assays, suggests that a Stem-Cell Compartment drives PTPRK-RSPO3 colorectal tumour growth and indicates that the therapeutic targeting of Stem-Cell properties within tumours may be a clinically relevant approach for the treatment of colorectal tumours.