Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System

Johansson, Clas B.; Momma, Stefan; Clarke, Diana L.; Risling, Mårten; Lendahl, Urban; Frisén, Jonas

doi:10.1016/s0092-8674(00)80956-3

Cited by 1,716 publications

(1,288 citation statements)

References 34 publications

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“…MicroRNA studies also suggest that SOX9 is gliogenic, promoting neural stem cells to adopt an astrocyte or oligodendrocyte fate (Cheng et al, 2009). Following injury, neural stem cells proliferate and differentiate almost exclusively into astrocytes (Johansson et al, 1999;Meletis et al, 2008) that generate scar, but not into neurons (Johansson et al, 1999). These results are consistent with the hypothesis that, in neural stem cells, SOX9 expression promotes a glial rather than a neuronal cell fate and that, in Sox9 conditional knock-outs, neural stem cells activated by the injury may adopt a neuronal as opposed to a glial fate.…”

Section: Discussionmentioning

confidence: 99%

Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury

McKillop

Dragan

Schedl

et al. 2012

Glia

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Chondroitin sulfate proteoglycans (CSPGs) found in perineuronal nets and in the glial scar after spinal cord injury have been shown to inhibit axonal growth and plasticity. Since we have previously identified SOX9 as a transcription factor that upregulates the expression of a battery of genes associated with glial scar formation in primary astrocyte cultures, we predicted that conditional Sox9 ablation would result in reduced CSPG expression after spinal cord injury and that this would lead to increased neuroplasticity and improved locomotor recovery. Control and Sox9 conditional knock-out mice were subject to a 70 kdyne contusion spinal cord injury at thoracic level 9. One week after injury, Sox9 conditional knock-out mice expressed reduced levels of CSPG biosynthetic enzymes (Xt-1 and C4st), CSPG core proteins (brevican, neurocan, and aggrecan), collagens 2a1 and 4a1, and Gfap, a marker of astrocyte activation, in the injured spinal cord compared with controls. These changes in gene expression were accompanied by improved hind limb function and locomotor recovery as evaluated by the Basso Mouse Scale (BMS) and rodent activity boxes. Histological assessments confirmed reduced CSPG deposition and collagenous scarring at the lesion of Sox9 conditional knock-out mice, and demonstrated increased neurofilament-positive fibers in the lesion penumbra and increased serotonin immunoreactivity caudal to the site of injury. These results suggest that SOX9 inhibition is a potential strategy for the treatment of SCI.

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Section: Discussionmentioning

confidence: 99%

Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury

McKillop

Dragan

Schedl

et al. 2012

Glia

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“…Mice were sacrificed and perfused at various times after BMT as described in Johansson et al 37 . Briefly, mice were deeply anesthetized and immediately perfused with PBS followed by ice-cold 4% paraformaldehyde in phosphate buffer and cryoprotected in sucrose/ phosphate buffer solution overnight (O/N).…”

Section: Perfusion Of Mice and Harvesting Of Cerebellummentioning

confidence: 99%

“…Mice are examined daily for clinical signs of EAE and scored as in Youssef et al 40 . The mice were perfused as described in Johansson et al 37 at either 44 or 65 days post EAE induction.…”

Section: Experimental Autoimmune Encephalomyelitis Inductionmentioning

confidence: 99%

Extensive fusion of haematopoietic cells with Purkinje neurons in response to chronic inflammation

et al. 2008

Self Cite

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Transplanted bone marrow derived cells (BMDCs) have been reported to fuse with cells of diverse tissues [1][2][3][4][5][6][7][8][9][10][11][12][13] , but the extremely low frequency of fusion has led to the view that such events are biologically insignificant. Nonetheless, in mice with a lethal recessive liver disease (tyrosinaemia), transplantation of wild type BMDCs restored liver function by cell fusion and rescued the mice from death 3, 9 , indicating that cell fusion can have beneficial effects. Here we report that chronic inflammation resulting from severe dermatitis or autoimmune encephalitis leads to robust fusion of BMDCs with Purkinje neurons and formation of hundreds of binucleate heterokaryons, a 10-100 fold higher frequency than previously reported 8,10,11,14 . Single haematopoietic stem cell transplants showed that the fusogenic cell is in the haematopoietic lineage and parabiosis experiments revealed that fusion can occur without irradiation. Species-mismatched bone marrow transplants resulted in activation of dormant rat Purkinje neuron-specific genes in BMDC nuclei post-fusion with mouse Purkinje neurons consistent with nuclear reprogramming. The precise neurological role of these heterokaryons awaits elucidation, but their frequency in brain after inflammation is clearly much higher than previously appreciated.Although fusion of like cells has long been known to accompany the normal development of a number of tissues such as skeletal muscle, bone and the placenta 15-17 , recent evidence from numerous laboratories indicates that bone marrow derived cells (BMDC) can fuse with

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“…Multipotent neural stem cells (NSCs) have been identified and isolated from mammalian central nervous system [4][5][6] including embryonic and adult human brain [7][8][9][10][11][12][13][14][15]. However, human NSC lines which could be useful in clinical setting are difficult to establish in vitro and, several different approaches have been developed to overcome this problem.…”

Section: Introductionmentioning

confidence: 99%

Generation of human cortical neurons from a new immortal fetal neural stem cell line

Cacci

Villa

Parmar

et al. 2007

Experimental Cell Research

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Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia. and neurons (mostly glutamatergic and GABAergic, as well as tyrosine hydroxylase-positive, presumably dopaminergic neurons). RT-PCR analysis showed that the hc-NSCs retained expression of Pax6, Emx2 and Neurogenin2, which are genes associated with regionalization and cell commitment in cortical precursors during brain development. Our data indicate that this hc-NSC line could be useful for exploring the potential of human NSCs to replace dead or damaged cortical cells in animal models of acute and chronic neurodegenerative diseases. Taking advantage of its clonality and homogeneity, this cell line will also be a valuable experimental tool to study the regulatory role of intrinsic and extrinsic factors in human NSC biology. (c) 2006 Elsevier Inc. All rights reserved

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Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System

Cited by 1,716 publications

References 34 publications

Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury

Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury

Extensive fusion of haematopoietic cells with Purkinje neurons in response to chronic inflammation

Generation of human cortical neurons from a new immortal fetal neural stem cell line

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