The Experts below are selected from a list of 3714 Experts worldwide ranked by ideXlab platform
Mor R Alkaslasi - One of the best experts on this subject based on the ideXlab platform.
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single nucleus rna sequencing defines unexpected diversity of Cholinergic Neuron types in the adult mouse spinal cord
Nature Communications, 2021Co-Authors: Mor R Alkaslasi, Zoe E Piccus, Hanna Silberberg, Li Chen, Yajun Zhang, Timothy J Petros, Sangeetha Hareendran, Claire Le E PichonAbstract:In vertebrates, motor control relies on Cholinergic Neurons in the spinal cord that have been extensively studied over the past hundred years, yet the full heterogeneity of these Neurons and their different functional roles in the adult remain to be defined. Here, we develop a targeted single nuclear RNA sequencing approach and use it to identify an array of Cholinergic interNeurons, visceral and skeletal motor Neurons. Our data expose markers for distinguishing these classes of Cholinergic Neurons and their rich diversity. Specifically, visceral motor Neurons, which provide autonomic control, can be divided into more than a dozen transcriptomic classes with anatomically restricted localization along the spinal cord. The complexity of the skeletal motor Neurons is also reflected in our analysis with alpha, gamma, and a third subtype, possibly corresponding to the elusive beta motor Neurons, clearly distinguished. In combination, our data provide a comprehensive transcriptomic description of this important population of Neurons that control many aspects of physiology and movement and encompass the cellular substrates for debilitating degenerative disorders.
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single nucleus rna sequencing defines unexpected diversity of Cholinergic Neuron types in the adult mouse spinal cord
bioRxiv, 2020Co-Authors: Mor R Alkaslasi, Zoe E Piccus, Hanna Silberberg, Li Chen, Yajun Zhang, Timothy J Petros, Claire Le E PichonAbstract:Abstract In vertebrates, motor control relies on Cholinergic Neurons in the spinal cord that have been extensively studied over the past hundred years, yet the full heterogeneity of these Neurons and their different functional roles in the adult remain to be defined. Here, we developed a targeted single nuclear RNA sequencing approach and used it to identify an array of Cholinergic interNeurons, visceral and skeletal motor Neurons. Our data expose markers for distinguishing these classes of Cholinergic Neurons and their extremely rich diversity. Specifically, visceral motor Neurons, which provide autonomic control, could be divided into more than a dozen transcriptomic classes with anatomically restricted localization along the spinal cord. The complexity of the skeletal motor Neurons was also reflected in our analysis with alpha, beta, and gamma subtypes clearly distinguished. In combination, our data provide a comprehensive transcriptomic description of this important population of Neurons that control many aspects of physiology and movement and encompass the cellular substrates for debilitating degenerative disorders.
Junying Miao - One of the best experts on this subject based on the ideXlab platform.
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Cholinergic Neuron like cells derived from bone marrow stromal cells induced by tricyclodecane 9 yl xanthogenate promote functional recovery and neural protection after spinal cord injury
Cell Transplantation, 2013Co-Authors: Chunhui Sun, Jing Shao, Jing Zhao, Shaonan Yang, Shangli Zhang, Jiangang Gao, Junying MiaoAbstract:The rate of Neuronal differentiation of bone marrow stromal cells (BMSCs) in vivo is very low; therefore, it is necessary to elevate the number of BMSC-derived Neurons to cure neurodegenerative diseases. We previously reported that tricyclodecane-9-yl-xanthogenate (D609), an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), induced BMSCs to differentiate into Neuron-like cells in vitro. However, the Neuronal type is not clear, and it is still unknown whether these Neuron-like cells possess physiological properties of functional Neurons and whether they can contribute to the recovery of Neuron dysfunction. To answer these questions, we investigated their characteristics by detecting Neuronal function-related neurotransmitters and calcium image. The results showed that these cells exhibited functional Cholinergic Neurons in vitro. Transplantation of these Cholinergic Neuron-like cells promoted the recovery of spinal cord-injured mice, and they were more effective than BMSCs. The number of Cholinergic Neurons was increased after injection with BMSC-derived Cholinergic Neuron-like cells, indicating their high differentiation rate in vivo. Moreover, the proportion of Cholinergic Neurons in host cells and secretion of acetylcholine were increased, and preservation of neurofilament was also observed in the lesion of mice implanted with BMSC-derived Neurons, suggesting the Neuronal protection of BMSC-derived Neurons. Our findings provide both a simple method to induce the differentiation of BMSCs into Cholinergic Neuron-like cells and a putative strategy for the therapy of spinal cord injuries.
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phosphatidylcholine specific phospholipase c heat shock protein 70 hsp70 transcription factor b cell translocation gene 2 signaling in rat bone marrow stromal cell differentiation to Cholinergic Neuron like cells
The International Journal of Biochemistry & Cell Biology, 2012Co-Authors: Jing Shao, Chunhui Sun, Jing Zhao, Shangli Zhang, Junying MiaoAbstract:Abstract Although bone marrow stromal cells (BMSCs) can differentiate into Neuron-like cells, the mechanisms underlying Neuronal differentiation are not well understood. We recently found that inhibition of phosphatidylcholine-specific phospholipase C (PC-PLC) by its inhibitor D609 promoted BMSCs’ differentiation into Cholinergic Neuron-like cells. Using the effective small molecule D609 and gene microarray technology, we investigated the change of gene expression profile to identify key mediators involved in the Neuronal differentiation. We selected heat shock protein 70 (Hsp70) and transcription factor B-cell translocation gene 2 (Btg2) that were maximally up-regulated for further study. We found that functional suppression of Hsp70 blocked D609-induced increase of Btg2 expression and Cholinergic Neuronal differentiation of BMSCs. These results demonstrated that Hsp70 was the pivotal factor in PC-PLC-medicated Neuronal differentiation of BMSCs, and Btg2 might be its downstream target. Our findings provide new clues for controlling BMSCs’ differentiation into Cholinergic Neuron-like cells and provide a putative strategy for neurodegenerative diseases therapies.
Claire Le E Pichon - One of the best experts on this subject based on the ideXlab platform.
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single nucleus rna sequencing defines unexpected diversity of Cholinergic Neuron types in the adult mouse spinal cord
Nature Communications, 2021Co-Authors: Mor R Alkaslasi, Zoe E Piccus, Hanna Silberberg, Li Chen, Yajun Zhang, Timothy J Petros, Sangeetha Hareendran, Claire Le E PichonAbstract:In vertebrates, motor control relies on Cholinergic Neurons in the spinal cord that have been extensively studied over the past hundred years, yet the full heterogeneity of these Neurons and their different functional roles in the adult remain to be defined. Here, we develop a targeted single nuclear RNA sequencing approach and use it to identify an array of Cholinergic interNeurons, visceral and skeletal motor Neurons. Our data expose markers for distinguishing these classes of Cholinergic Neurons and their rich diversity. Specifically, visceral motor Neurons, which provide autonomic control, can be divided into more than a dozen transcriptomic classes with anatomically restricted localization along the spinal cord. The complexity of the skeletal motor Neurons is also reflected in our analysis with alpha, gamma, and a third subtype, possibly corresponding to the elusive beta motor Neurons, clearly distinguished. In combination, our data provide a comprehensive transcriptomic description of this important population of Neurons that control many aspects of physiology and movement and encompass the cellular substrates for debilitating degenerative disorders.
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single nucleus rna sequencing defines unexpected diversity of Cholinergic Neuron types in the adult mouse spinal cord
bioRxiv, 2020Co-Authors: Mor R Alkaslasi, Zoe E Piccus, Hanna Silberberg, Li Chen, Yajun Zhang, Timothy J Petros, Claire Le E PichonAbstract:Abstract In vertebrates, motor control relies on Cholinergic Neurons in the spinal cord that have been extensively studied over the past hundred years, yet the full heterogeneity of these Neurons and their different functional roles in the adult remain to be defined. Here, we developed a targeted single nuclear RNA sequencing approach and used it to identify an array of Cholinergic interNeurons, visceral and skeletal motor Neurons. Our data expose markers for distinguishing these classes of Cholinergic Neurons and their extremely rich diversity. Specifically, visceral motor Neurons, which provide autonomic control, could be divided into more than a dozen transcriptomic classes with anatomically restricted localization along the spinal cord. The complexity of the skeletal motor Neurons was also reflected in our analysis with alpha, beta, and gamma subtypes clearly distinguished. In combination, our data provide a comprehensive transcriptomic description of this important population of Neurons that control many aspects of physiology and movement and encompass the cellular substrates for debilitating degenerative disorders.
Anders Bjorklund - One of the best experts on this subject based on the ideXlab platform.
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ex vivo nerve growth factor gene transfer to the basal forebrain in presymptomatic middle aged rats prevents the development of Cholinergic Neuron atrophy and cognitive impairment during aging
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Alberto Martinezserrano, Anders BjorklundAbstract:Nerve growth factor (NGF) is able to restore spatial learning and reverse forebrain Cholinergic Neuron atrophy when administered intracerebrally to behaviorally impaired aged rats. In the present study, behaviorally unimpaired, middle-aged rats (14–16 months old) received transplants of ex vivo transduced, clonal NGF-secreting immortalized neural progenitor cells, bilaterally in the nucleus basalis and septum. During the subsequent 9 months the aged control animals developed the expected impairment in spatial learning in the water maze task, whereas the animals with NGF-secreting grafts maintained a performance level not different from the 12-month-old control rats. The marked age-induced atrophy (−25%) of the Cholinergic Neurons in medial septum and nucleus basalis, seen in the aged control rats, was not present in the NGF-treated aged animals. 3H-labeled thymidine autoradiography showed that the transduced cells survived well and had become integrated into the host tissue surrounding the injection sites, and reverse transcription–PCR analysis revealed expression of the NGF transgene, at both 4 and 9 months postgrafting, in the grafted tissue. The results show that long-term supply of NGF from ex vivo transduced immortalized neural progenitor cells locally within the nucleus basalis and septum can prevent the subsequent development of age-dependent Neuronal atrophy and behavioral impairments when the animals reach advanced age.
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ex vivo nerve growth factor gene transfer to the basal forebrain in presymptomatic middle aged rats prevents the development of Cholinergic Neuron atrophy and cognitive impairment during aging gene therapyyalzheimer s diseaseymemoryyp75ntr
1998Co-Authors: Alberto Martinezserrano, Anders BjorklundAbstract:Nerve growth factor (NGF) is able to restore spatial learning and reverse forebrain Cholinergic Neuron atro- phy when administered intracerebrally to behaviorally impaired aged rats. In the present study, behaviorally unimpaired, middle- aged rats (14-16 months old) received transplants of ex vivo transduced, clonal NGF-secreting immortalized neural progen- itor cells, bilaterally in the nucleus basalis and septum. During the subsequent 9 months the aged control animals developed the expected impairment in spatial learning in the water maze task, whereas the animals with NGF-secreting grafts maintained a performance level not different from the 12-month-old control rats. The marked age-induced atrophy (225%) of the Cholinergic Neurons in medial septum and nucleus basalis, seen in the aged control rats, was not present in the NGF-treated aged animals. 3 H-labeled thymidine autoradiography showed that the trans- duced cells survived well and had become integrated into the host tissue surrounding the injection sites, and reverse transcription- PCR analysis revealed expression of the NGF transgene, at both 4 and 9 months postgrafting, in the grafted tissue. The results show that long-term supply of NGF from ex vivo transduced immortalized neural progenitor cells locally within the nucleus basalis and septum can prevent the subsequent development of age-dependent Neuronal atrophy and behavioral impairments when the animals reach advanced age. Studies in rodents have shown that the basal forebrain Cholinergic system undergoes progressive degenerative changes with advanc- ing age, and that the magnitude of these changes generally is
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reversal of age dependent cognitive impairments and Cholinergic Neuron atrophy by ngf secreting neural progenitors grafted to the basal forebrain
Neuron, 1995Co-Authors: Alberto Martinezserrano, Walter Fischer, Anders BjorklundAbstract:Abstract A highly NGF-secreting cell line was generated by retroviral transduction of a conditionally immortalized CNS-derived neural progenitor cell line. After transplantation to the nucleus basalls magnocellularis (NBM), the cells continue to express the NGF transgene for at least 10 weeks, producing sufficient NGF to reverse Cholinergic Neuron atrophy in aged rats and induce cellular hypertrophy In young rats. In cognitively impaired aged rats, transplants of the NGF-secreting cells placed either In the NBM and septum or in only the NBM induced a near-complete reversal of the spatial learning impairment. This was accompanied by a normalization of the size of the Cholinergic Neurons in the grafted areas. The results demonstrate that locally increased supply of NGF to the basal forebrain Cholinergic nuclei has a significant Impact on cognitive function and support the usefulness of neural progenitor cells for long-term localized delivery of neurotrophins to the CNS.
Zoe E Piccus - One of the best experts on this subject based on the ideXlab platform.
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single nucleus rna sequencing defines unexpected diversity of Cholinergic Neuron types in the adult mouse spinal cord
Nature Communications, 2021Co-Authors: Mor R Alkaslasi, Zoe E Piccus, Hanna Silberberg, Li Chen, Yajun Zhang, Timothy J Petros, Sangeetha Hareendran, Claire Le E PichonAbstract:In vertebrates, motor control relies on Cholinergic Neurons in the spinal cord that have been extensively studied over the past hundred years, yet the full heterogeneity of these Neurons and their different functional roles in the adult remain to be defined. Here, we develop a targeted single nuclear RNA sequencing approach and use it to identify an array of Cholinergic interNeurons, visceral and skeletal motor Neurons. Our data expose markers for distinguishing these classes of Cholinergic Neurons and their rich diversity. Specifically, visceral motor Neurons, which provide autonomic control, can be divided into more than a dozen transcriptomic classes with anatomically restricted localization along the spinal cord. The complexity of the skeletal motor Neurons is also reflected in our analysis with alpha, gamma, and a third subtype, possibly corresponding to the elusive beta motor Neurons, clearly distinguished. In combination, our data provide a comprehensive transcriptomic description of this important population of Neurons that control many aspects of physiology and movement and encompass the cellular substrates for debilitating degenerative disorders.
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single nucleus rna sequencing defines unexpected diversity of Cholinergic Neuron types in the adult mouse spinal cord
bioRxiv, 2020Co-Authors: Mor R Alkaslasi, Zoe E Piccus, Hanna Silberberg, Li Chen, Yajun Zhang, Timothy J Petros, Claire Le E PichonAbstract:Abstract In vertebrates, motor control relies on Cholinergic Neurons in the spinal cord that have been extensively studied over the past hundred years, yet the full heterogeneity of these Neurons and their different functional roles in the adult remain to be defined. Here, we developed a targeted single nuclear RNA sequencing approach and used it to identify an array of Cholinergic interNeurons, visceral and skeletal motor Neurons. Our data expose markers for distinguishing these classes of Cholinergic Neurons and their extremely rich diversity. Specifically, visceral motor Neurons, which provide autonomic control, could be divided into more than a dozen transcriptomic classes with anatomically restricted localization along the spinal cord. The complexity of the skeletal motor Neurons was also reflected in our analysis with alpha, beta, and gamma subtypes clearly distinguished. In combination, our data provide a comprehensive transcriptomic description of this important population of Neurons that control many aspects of physiology and movement and encompass the cellular substrates for debilitating degenerative disorders.