Intrinsic Control of Axon Regeneration

Neuron, Journal Year: 2016, Volume and Issue: 90(3), P. 437 - 451

Published: May 1, 2016

Language: Английский

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Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes

Neuron, Journal Year: 2019, Volume and Issue: 104(6), P. 1039 - 1055.e12

Published: Nov. 26, 2019

Language: Английский

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Intrinsic mechanisms of neuronal axon regeneration

Nature reviews. Neuroscience, Journal Year: 2018, Volume and Issue: 19(6), P. 323 - 337

Published: April 17, 2018

Language: Английский

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Subtype-Specific Regeneration of Retinal Ganglion Cells following Axotomy: Effects of Osteopontin and mTOR Signaling

Neuron, Journal Year: 2015, Volume and Issue: 85(6), P. 1244 - 1256

Published: March 1, 2015

Language: Английский

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CRISPR Interference-Based Platform for Multimodal Genetic Screens in Human iPSC-Derived Neurons

Neuron, Journal Year: 2019, Volume and Issue: 104(2), P. 239 - 255.e12

Published: Aug. 15, 2019

Highlights•A CRISPR interference platform for genetic screens in human iPSC-derived neurons•Survival uncover genes essential neurons, but not iPSCs or cancer cells•Single-cell RNA-seq reveal distinct neuronal roles ubiquitous genes•Arrayed high-content controlling morphologySummaryCRISPR/Cas9-based functional genomics have transformed our ability to elucidate mammalian cell biology. However, most previous CRISPR-based were conducted lines rather than healthy, differentiated cells. Here, we describe a (CRISPRi)-based neurons derived from induced pluripotent stem cells (iPSCs). We demonstrate robust and durable knockdown of endogenous such present results three complementary screens. First, survival-based screen revealed neuron-specific that improved survival upon knockdown. Second, with single-cell transcriptomic readout uncovered several examples whose had strikingly cell-type-specific consequences. Third, longitudinal imaging detected consequences gene on morphology. Our highlight the power unbiased types provide systematic interrogation normal disease states neurons.Video Abstract/cms/asset/c2672569-5397-4e97-a52a-74b50c33ac04/mmc10.mp4Loading ...Download video (mp4, 134 MB)Graphical abstract

Language: Английский

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CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury

Cell, Journal Year: 2019, Volume and Issue: 176(5), P. 1143 - 1157.e13

Published: Feb. 1, 2019

Language: Английский

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Short Hairpin RNA against PTEN Enhances Regenerative Growth of Corticospinal Tract Axons after Spinal Cord Injury

Journal of Neuroscience, Journal Year: 2013, Volume and Issue: 33(39), P. 15350 - 15361

Published: Sept. 25, 2013

Developing approaches to promote the regeneration of descending supraspinal axons represents an ideal strategy for rebuilding neuronal circuits improve functional recovery after spinal cord injury (SCI). Our previous studies demonstrated that genetic deletion phosphatase and tensin homolog (PTEN) in mouse corticospinal neurons reactivates their regenerative capacity, resulting significant tract (CST) SCI. However, it is unknown whether nongenetic methods suppressing PTEN have similar effects how regenerating interact with extrinsic environment. Herein, we show expression short-hairpin RNA (shRNA) promotes injured CST axons, these form anatomical synapses appropriate areas caudal lesion. Importantly, this model increased regrowth enables analysis regulators vivo . We find avoid dense clusters fibroblasts macrophages lesion, suggesting cell types might be key inhibitors axon regeneration. Furthermore, most cross lesion association astrocytes, indicating cells important providing a permissive bridge Lineage reveals bridge-forming astrocytes are not derived from ependymal stem within cord, they more likely subset mature astrocytes. Overall, study insights into critical intrinsic establishes shRNA as viable means manipulate translate findings other mammalian models.

Language: Английский

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Axon–soma communication in neuronal injury

Nature reviews. Neuroscience, Journal Year: 2013, Volume and Issue: 15(1), P. 32 - 42

Published: Dec. 11, 2013

Language: Английский

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Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death

Proceedings of the National Academy of Sciences, Journal Year: 2013, Volume and Issue: 110(10), P. 4045 - 4050

Published: Feb. 19, 2013

Glaucoma, a major cause of blindness worldwide, is neurodegenerative optic neuropathy in which vision loss caused by retinal ganglion cells (RGCs). To better define the pathways mediating RGC death and identify targets for development neuroprotective drugs, we developed high-throughput RNA interference screen with primary RGCs used it to full mouse kinome. The identified dual leucine zipper kinase (DLK) as key target RGCs. In cultured RGCs, DLK signaling both necessary sufficient cell death. undergoes robust posttranscriptional up-regulation response axonal injury vitro vivo. Using conditional knockout approach, confirmed that required JNK activation rodent model neuropathy. addition, tozasertib, small molecule protein inhibitor activity against DLK, protects from glaucoma traumatic models. Together, our results establish previously undescribed drug/drug combination glaucoma, an early marker injury, provide starting point more specific inhibitors treatment nonglaucomatous forms neuropathy, perhaps other CNS neurodegenerations.

Language: Английский

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Injury-Induced Decline of Intrinsic Regenerative Ability Revealed by Quantitative Proteomics

Neuron, Journal Year: 2015, Volume and Issue: 86(4), P. 1000 - 1014

Published: May 1, 2015

Language: Английский

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