摘要:
The present invention relates to culture systems comprising differentiated stem cells, that may be used for identifying agents useful in treating degenerative nervous system disorders and are suitable for high-throughput screening applications. It is based, at least in part, on the discovery that co-cultures of (i) astrocytes expressing a mutated SODI gene and (ii) stem-cell derived motor neurons manifested cell death via a Bax-dependent mechanism, and modeled motor neuron death in amyotrophic lateral sclerosis.
摘要:
Disclosed are methods for generating a neuron expressing Hoxc8 transcription factor or a caudal motor neuron comprising culturing an embryonic stem cell in a composition which is essentially free of retinoids and comprises an isotonic salt solution, so as to generate the neuron which expresses Hoxc8 transcription factor or the caudal motor neuron. Disclosed are also methods for generating a caudal brachial motor neuron, a thoracic motor neuron, or a lumbar motor neuron from an embryonic stem cell in a composition essentially free of retinoids and comprising ADFNK medium, an amount of FGF-2, or Gdf11 respectively. Disclosed are also methods of transplanting a motor neuron into a subject comprising generating the motor neuron and transplanting the motor neuron into the subject. Disclosed is also a population of motor neuron cells enriched for motor neuron cells expressing Foxp1 and expressing a gene associated with Spinal Muscular Atrophy (SMA) or Amyotrophic Lateral Sclerosis (ALS).
摘要:
The present invention provides a method for inducing differentiation of an embryonic stem cell into a differentiated neural cell. The present invention further provides a method for producing differentiated neural cells, and a population of cells comprising the differentiated neural cells. Additionally, the present invention provides a method for repopulating a spinal cord in a subject, and a method for treating nervous tissue degeneration in a subject in need of treatment. The present invention further provides neural progenitor cells, differentiated neural cells, and uses of same. Also provided is a transgenic non-human animal containing the differentiated neural cells. The present invention is further directed to a method for isolating a population of differentiated neural cells. Finally, the present invention provides a method for identifying an agent for use in treating a condition associated with neuron degeneration.
摘要:
The present invention relates to culture systems comprising differentiated stem cells, that may be used for identifying agents useful in treating degenerative nervous system disorders and are suitable for high-throughput screening applications. It is based, at least in part, on the discovery that co-cultures of (i) astrocytes expressing a mutated SODI gene and (ii) stem-cell derived motor neurons manifested cell death via a Bax-dependent mechanism, and modeled motor neuron death in amyotrophic lateral sclerosis.
摘要:
The present invention provides, inter alia, methods for identifying a candidate agent that may be effective to treat or ameliorate an effect of a neurodegenerative disease in a subject. These methods include: (a) contacting a wildtype neuron and a mutant neuron with a stressor which is effective to accelerate the degeneration of the mutant neuron; (b) further contacting the wildtype neuron and the mutant neuron from step (a) with a candidate agent; and (c) determining whether the candidate agent lowers a wildtype to mutant survival ratio or increases both wildtype and mutant neuron survival.
摘要:
The present invention provides, inter alia, methods for identifying a candidate agent that may be effective to treat or ameliorate an effect of a neurodegenerative disease in a subject. These methods include: (a) contacting a wildtype neuron and a mutant neuron with a stressor which is effective to accelerate the degeneration of the mutant neuron; (b) further contacting the wildtype neuron and the mutant neuron from step (a) with a candidate agent; and (c) determining whether the candidate agent lowers a wildtype to mutant survival ratio or increases both wildtype and mutant neuron survival.
摘要:
Disclosed are methods for generating a neuron expressing Hoxc8 transcription factor or a caudal motor neuron comprising culturing an embryonic stem cell in a composition which is essentially free of retinoids and comprises an isotonic salt solution, so as to generate the neuron which expresses Hoxc8 transcription factor or the caudal motor neuron. Disclosed are also methods for generating a caudal brachial motor neuron, a thoracic motor neuron, or a lumbar motor neuron from an embryonic stem cell in a composition essentially free of retinoids and comprising ADFNK medium, an amount of FGF-2, or Gdf11 respectively. Disclosed are also methods of transplanting a motor neuron into a subject comprising generating the motor neuron and transplanting the motor neuron into the subject. Disclosed is also a population of motor neuron cells enriched for motor neuron cells expressing Foxp1 and expressing a gene associated with Spinal Muscular Atrophy (SMA) or Amyotrophic Lateral Sclerosis (ALS).
摘要:
The present invention provides in vitro systems for use in identifying modulators of neural differentiation. Also provided are modulators identified by these systems. The present invention further provides methods for identifying a modulator of neural differentiation, a modulator of a Wnt signalling pathway, a modulator of Wnt-dependent neural differentiation, a modulator of a BMP signalling pathway, a modulator of BMP-dependent neural differentiation, a modulator of a Hh signalling pathway, and a modulator of Hh-dependent neural differentiation. Also provided are modulators identified by these methods.
摘要:
The present invention provides in vitro systems for use in identifying modulators of neural differentiation. Also provided are modulators identified by these systems. The present invention further provides methods for identifying a modulator of neural differentiation, a modulator of an FGF signalling pathway, a modulator of FGF-dependent neural differentiation, a modulator of a retinoid signalling pathway, and a modulator of retinoid-dependent neural differentiation. Also provided are modulators identified by these methods.
摘要:
The present invention provides in vitro systems for use in identifying modulators of neural differentiation. Also provided are modulators identified by these systems. The present invention further provides methods for identifying a modulator of neural differentiation, a modulator of a Wnt signalling pathway, a modulator of Wnt-dependent neural differentiation, a modulator of a BMP signalling pathway, a modulator of BMP-dependent neural differentiation, a modulator of a Hh signalling pathway, and a modulator of Hh-dependent neural differentiation. Also provided are modulators identified by these methods.