The Experts below are selected from a list of 2811 Experts worldwide ranked by ideXlab platform
Ling Chen - One of the best experts on this subject based on the ideXlab platform.
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Seipin knockout in mice impairs stem cell proliferation and progenitor cell differentiation in the adult hippocampal dentate gyrus via reduced levels of PPARγ
Disease models & mechanisms, 2015Co-Authors: Ying Zhu, Conghui Wang, Sha Sha, Libin Zhou, Xunde Xian, George Liu, Ling ChenAbstract:The seipin gene ( BSCL2 ) was originally identified in humans as a loss-of-function gene associated with congenital generalized lipodystrophy type 2 (CGL2). Neuronal seipin-knockout (seipin-nKO) mice display a depression-like phenotype with a reduced level of hippocampal peroxisome proliferator-activated receptor gamma (PPARγ). The present study investigated the influence of seipin deficiency on adult neurogenesis in the hippocampal dentate gyrus (DG) and the underlying mechanisms of the effects. We show that the proliferative capability of stem cells in seipin-nKO mice was substantially reduced compared to in wild-type (WT) mice, and that this could be rescued by the PPARγ agonist rosiglitazone (rosi). In seipin-nKO mice, neuronal differentiation of progenitor cells was inhibited, with the enhancement of astrogliogenesis; both of these effects were recovered by rosi treatment during early stages of progenitor cell differentiation. In addition, rosi treatment could correct the decline in hippocampal ERK2 phosphorylation and cyclin A mRNA level in seipin-nKO mice. The MEK inhibitor U0126 abolished the rosi-rescued cell proliferation and cyclin A expression in seipin-nKO mice. In seipin-nKO mice, the hippocampal Wnt3 protein level was less than that in WT mice, and there was a reduction of Neurogenin 1 ( Neurog1 ) and neurogenic differentiation 1 ( NeuroD1 ) mRNA, levels of which were corrected by rosi treatment. STAT3 phosphorylation (Tyr705) was enhanced in seipin-nKO mice, and was further elevated by rosi treatment. Finally, rosi treatment for 10 days could alleviate the depression-like phenotype in seipin-nKO mice, and this alleviation was blocked by the MEK inhibitor U0126. The results indicate that, by reducing PPARγ, seipin deficiency impairs proliferation and differentiation of neural stem and progenitor cells, respectively, in the adult DG, which might be responsible for the production of the depression-like phenotype in seipin-nKO mice.
Libin Zhou - One of the best experts on this subject based on the ideXlab platform.
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Seipin knockout in mice impairs stem cell proliferation and progenitor cell differentiation in the adult hippocampal dentate gyrus via reduced levels of PPARγ
Disease models & mechanisms, 2015Co-Authors: Ying Zhu, Conghui Wang, Sha Sha, Libin Zhou, Xunde Xian, George Liu, Ling ChenAbstract:The seipin gene ( BSCL2 ) was originally identified in humans as a loss-of-function gene associated with congenital generalized lipodystrophy type 2 (CGL2). Neuronal seipin-knockout (seipin-nKO) mice display a depression-like phenotype with a reduced level of hippocampal peroxisome proliferator-activated receptor gamma (PPARγ). The present study investigated the influence of seipin deficiency on adult neurogenesis in the hippocampal dentate gyrus (DG) and the underlying mechanisms of the effects. We show that the proliferative capability of stem cells in seipin-nKO mice was substantially reduced compared to in wild-type (WT) mice, and that this could be rescued by the PPARγ agonist rosiglitazone (rosi). In seipin-nKO mice, neuronal differentiation of progenitor cells was inhibited, with the enhancement of astrogliogenesis; both of these effects were recovered by rosi treatment during early stages of progenitor cell differentiation. In addition, rosi treatment could correct the decline in hippocampal ERK2 phosphorylation and cyclin A mRNA level in seipin-nKO mice. The MEK inhibitor U0126 abolished the rosi-rescued cell proliferation and cyclin A expression in seipin-nKO mice. In seipin-nKO mice, the hippocampal Wnt3 protein level was less than that in WT mice, and there was a reduction of Neurogenin 1 ( Neurog1 ) and neurogenic differentiation 1 ( NeuroD1 ) mRNA, levels of which were corrected by rosi treatment. STAT3 phosphorylation (Tyr705) was enhanced in seipin-nKO mice, and was further elevated by rosi treatment. Finally, rosi treatment for 10 days could alleviate the depression-like phenotype in seipin-nKO mice, and this alleviation was blocked by the MEK inhibitor U0126. The results indicate that, by reducing PPARγ, seipin deficiency impairs proliferation and differentiation of neural stem and progenitor cells, respectively, in the adult DG, which might be responsible for the production of the depression-like phenotype in seipin-nKO mice.
Sha Sha - One of the best experts on this subject based on the ideXlab platform.
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Seipin knockout in mice impairs stem cell proliferation and progenitor cell differentiation in the adult hippocampal dentate gyrus via reduced levels of PPARγ
Disease models & mechanisms, 2015Co-Authors: Ying Zhu, Conghui Wang, Sha Sha, Libin Zhou, Xunde Xian, George Liu, Ling ChenAbstract:The seipin gene ( BSCL2 ) was originally identified in humans as a loss-of-function gene associated with congenital generalized lipodystrophy type 2 (CGL2). Neuronal seipin-knockout (seipin-nKO) mice display a depression-like phenotype with a reduced level of hippocampal peroxisome proliferator-activated receptor gamma (PPARγ). The present study investigated the influence of seipin deficiency on adult neurogenesis in the hippocampal dentate gyrus (DG) and the underlying mechanisms of the effects. We show that the proliferative capability of stem cells in seipin-nKO mice was substantially reduced compared to in wild-type (WT) mice, and that this could be rescued by the PPARγ agonist rosiglitazone (rosi). In seipin-nKO mice, neuronal differentiation of progenitor cells was inhibited, with the enhancement of astrogliogenesis; both of these effects were recovered by rosi treatment during early stages of progenitor cell differentiation. In addition, rosi treatment could correct the decline in hippocampal ERK2 phosphorylation and cyclin A mRNA level in seipin-nKO mice. The MEK inhibitor U0126 abolished the rosi-rescued cell proliferation and cyclin A expression in seipin-nKO mice. In seipin-nKO mice, the hippocampal Wnt3 protein level was less than that in WT mice, and there was a reduction of Neurogenin 1 ( Neurog1 ) and neurogenic differentiation 1 ( NeuroD1 ) mRNA, levels of which were corrected by rosi treatment. STAT3 phosphorylation (Tyr705) was enhanced in seipin-nKO mice, and was further elevated by rosi treatment. Finally, rosi treatment for 10 days could alleviate the depression-like phenotype in seipin-nKO mice, and this alleviation was blocked by the MEK inhibitor U0126. The results indicate that, by reducing PPARγ, seipin deficiency impairs proliferation and differentiation of neural stem and progenitor cells, respectively, in the adult DG, which might be responsible for the production of the depression-like phenotype in seipin-nKO mice.
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Seipin knockout in mice impairs stem cell proliferation and progenitor cell differentiation in the adult hippocampal dentate gyrus via reduced levels of PPAR gamma
DISEASE MODELS & MECHANISMS, 2015Co-Authors: Li Guoxi, Sha Sha, Zhou Libin, Zhu Ying, Wang Conghui, Xian Xunde, Ji Yong, Liu George, Chen LingAbstract:The seipin gene (BSCL2) was originally identified in humans as a loss-of-function gene associated with congenital generalized lipodystrophy type 2 (CGL2). Neuronal seipin-knockout (seipinn-KO) mice display a depression-like phenotype with a reduced level of hippocampal peroxisome proliferator-activated receptor gamma (PPAR.). The present study investigated the influence of seipin deficiency on adult neurogenesis in the hippocampal dentate gyrus (DG) and the underlying mechanisms of the effects. We show that the proliferative capability of stem cells in seipin-nKO mice was substantially reduced compared to in wild-type (WT) mice, and that this could be rescued by the PPAR. agonist rosiglitazone (rosi). In seipin-nKO mice, neuronal differentiation of progenitor cells was inhibited, with the enhancement of astrogliogenesis; both of these effects were recovered by rosi treatment during early stages of progenitor cell differentiation. In addition, rosi treatment could correct the decline in hippocampal ERK2 phosphorylation and cyclin A mRNA level in seipin-nKO mice. The MEK inhibitor U0126 abolished the rosi-rescued cell proliferation and cyclin A expression in seipin-nKO mice. In seipin-nKO mice, the hippocampal Wnt3 protein level was less than that in WT mice, and there was a reduction of Neurogenin 1 (Neurog1) and neurogenic differentiation 1 (NeuroD1) mRNA, levels of which were corrected by rosi treatment. STAT3 phosphorylation (Tyr705) was enhanced in seipin-nKO mice, and was further elevated by rosi treatment. Finally, rosi treatment for 10 days could alleviate the depression-like phenotype in seipin-nKO mice, and this alleviation was blocked by the MEK inhibitor U0126. The results indicate that, by reducing PPAR., seipin deficiency impairs proliferation and differentiation of neural stem and progenitor cells, respectively, in the adult DG, which might be responsible for the production of the depression-like phenotype in seipin-nKO mice.grant for National 973 Basic Research Program of Chinese Ministry of Science and Technology [2014CB943303]; grant for National Natural Science Foundation of China [81361120247, 31171440, 81471157]SCI(E)PubMedARTICLEgeorgeliu@bjmu.edu.cn; lingchen@njmu.edu.cn121615-1624
R. Keith Duncan - One of the best experts on this subject based on the ideXlab platform.
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BDNF profoundly and specifically increases KCNQ4 expression in neurons derived from embryonic stem cells
Stem cell research, 2012Co-Authors: Erin K. Purcell, Liqian Liu, Amy Yang, J. Matthew Velkey, Marti M. Morales, R. Keith DuncanAbstract:Abstract Neurons resembling the spiral ganglion neurons (SGNs) of the auditory nerve can be generated from embryonic stem cells through induced overexpression of the transcription factor Neurogenin-1 (Neurog1). While recapitulating this developmental pathway produces glutamatergic, bipolar neurons reminiscent of SGNs, these neurons are functionally immature, being characterized by a depolarized resting potential and limited excitability. We explored the effects of two neurotrophins known to be present in the inner ear, brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), on the electrophysiology of neurons following Neurog1 induction. Our data reveal a significant reduction in resting membrane potential (RMP) following neurotrophin exposure, with BDNF producing a more robust effect than NT-3. This effect was accompanied by a profound and specific upregulation of the KCNQ4 subtype, where a 9-fold increase was observed with quantitative PCR. The other neuronally expressed KCNQ subtypes (2, 3, and 5) exhibited upregulation which was 3-fold or less in magnitude. Quantitative immunohistochemistry confirmed the increase in KCNQ4 expression at the protein level. The present data show a novel link between BDNF and KCNQ4 expression, yielding insight into the restricted expression pattern of a channel known to play special roles in setting the resting potential of auditory cells and in the etiology of progressive high‐frequency hearing loss.
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The intrinsic electrophysiological properties of neurons derived from mouse embryonic stem cells overexpressing Neurogenin-1.
American journal of physiology. Cell physiology, 2010Co-Authors: Mingjie Tong, Erin K. Purcell, Richard A. Altschuler, Jeannie L. Hernandez, R. Keith DuncanAbstract:A mouse embryonic stem (ES) cell line containing an inducible transgene for the proneural gene Neurog1 has been used to generate glutamatergic neurons at a high efficiency. The present study used i...
Erin K. Purcell - One of the best experts on this subject based on the ideXlab platform.
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BDNF profoundly and specifically increases KCNQ4 expression in neurons derived from embryonic stem cells
Stem cell research, 2012Co-Authors: Erin K. Purcell, Liqian Liu, Amy Yang, J. Matthew Velkey, Marti M. Morales, R. Keith DuncanAbstract:Abstract Neurons resembling the spiral ganglion neurons (SGNs) of the auditory nerve can be generated from embryonic stem cells through induced overexpression of the transcription factor Neurogenin-1 (Neurog1). While recapitulating this developmental pathway produces glutamatergic, bipolar neurons reminiscent of SGNs, these neurons are functionally immature, being characterized by a depolarized resting potential and limited excitability. We explored the effects of two neurotrophins known to be present in the inner ear, brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), on the electrophysiology of neurons following Neurog1 induction. Our data reveal a significant reduction in resting membrane potential (RMP) following neurotrophin exposure, with BDNF producing a more robust effect than NT-3. This effect was accompanied by a profound and specific upregulation of the KCNQ4 subtype, where a 9-fold increase was observed with quantitative PCR. The other neuronally expressed KCNQ subtypes (2, 3, and 5) exhibited upregulation which was 3-fold or less in magnitude. Quantitative immunohistochemistry confirmed the increase in KCNQ4 expression at the protein level. The present data show a novel link between BDNF and KCNQ4 expression, yielding insight into the restricted expression pattern of a channel known to play special roles in setting the resting potential of auditory cells and in the etiology of progressive high‐frequency hearing loss.
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Netrin-1-mediated axon guidance in mouse embryonic stem cells overexpressing Neurogenin-1.
Stem cells and development, 2012Co-Authors: Gerhard W. Hill, Erin K. Purcell, Liqian Liu, John Matthew Velkey, Richard A. Altschuler, Robert Keith DuncanAbstract:Stem cell therapy holds great promise for treating neurodegenerative disease, but major barriers to effective therapeutic strategies remain. A complete understanding of the derived phenotype is required for predicting cell response once introduced into the host tissue. We sought to identify major axonal guidance cues present in neurons derived from the transient overexpression of Neurogenin-1 (Neurog1) in mouse embryonic stem cells (ESCs). Neurog1 upregulated the netrin-1 axon guidance receptors DCC (deleted in colorectal cancer) and neogenin (NEO1). Quantitative polymerase chain reaction results showed a 2-fold increase in NEO1 mRNA and a 36-fold increase in DCC mRNA in Neurog1-induced compared with control ESCs. Immunohistochemistry indicated that DCC was primarily expressed on cells positive for the neuronal marker TUJ1. DCC was preferentially localized to the cell soma and growth-cones of induced neurons. In contrast, NEO1 expression showed less specificity, labeling both TUJ1-positive and TUJ1-negati...
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The intrinsic electrophysiological properties of neurons derived from mouse embryonic stem cells overexpressing Neurogenin-1.
American journal of physiology. Cell physiology, 2010Co-Authors: Mingjie Tong, Erin K. Purcell, Richard A. Altschuler, Jeannie L. Hernandez, R. Keith DuncanAbstract:A mouse embryonic stem (ES) cell line containing an inducible transgene for the proneural gene Neurog1 has been used to generate glutamatergic neurons at a high efficiency. The present study used i...