Reactive Glia in the Injured Brain Acquire Stem Cell Properties in Response to Sonic Hedgehog

Sirko, S.; Behrendt, Gwendolyn; Johansson, Peter; Tripathi, Pratibha; Costa, Marcos Romualdo; Bek, Sarah; Heinrich, Christophe; Tiedt, Steffen; Colak, Dilek; Dichgans, Martin; Fischer, Isabel Rebekka; Plesnila, Nikolaus; Staufenbiel, Matthias; Haass, Christian; Snapyan, Marina; Saghatelyan, Armen; Tsai, Li Huei; Fischer, André; Grobe, Kay; Dimou, Leda; Götz, Magdalena

doi:10.1016/j.stem.2013.04.007

Cited by 119 publications

(270 citation statements)

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“…Thus, after the initial 'expansion' phase of setting up the stem/ progenitor cell pool in the two neurogenic niches, SHH may Mature astrocytes and NSCs share many molecular and morphological characteristics, and both cell types respond to sonic hedgehog (SHH) signaling. Whether one cell type can be transformed into the other (dashed double-headed arrow), as appears to occur during injury (Sirko et al, 2013), and what role HH signaling may play in this process remain to be determined. NSCs also produce a small number of oligodendrocytes (gray), which is augmented by SHH signaling (Loulier et al, 2006).…”

Section: Fig 1 Mechanism Of Canonical Hh Signal Transduction In Vermentioning

confidence: 99%

“…Postnatal removal of Smo in astrocytes results in a partial reactive astrogliosislike phenotype (Garcia et al, 2010), which would normally occur only after CNS injury or in disease (Sofroniew, 2009). Recently, the precise level of SHH signaling was shown to be crucial for the induction of reactive astrogliosis in response to invasive brain injury, as both inhibition and stimulation of the pathway resulted in reactive astrocytes (Sirko et al, 2013). Interestingly, however, only SHH augmentation was able to trigger proliferative and neurosphere-forming abilities in cortical astrocytes.…”

Section: Fig 1 Mechanism Of Canonical Hh Signal Transduction In Vermentioning

confidence: 99%

“…Interestingly, however, only SHH augmentation was able to trigger proliferative and neurosphere-forming abilities in cortical astrocytes. This result is particularly intriguing as a separate study has shown that reactive astrocytes can be directly converted to functional neurons in vivo (Guo et al, 2013;Sirko et al, 2013). Thus, although the precise role of SHH signaling in maintaining parenchymal astrocyte function is unclear, SHH seems to act as a modulator of brain plasticity and regeneration.…”

Section: Fig 1 Mechanism Of Canonical Hh Signal Transduction In Vermentioning

confidence: 99%

“…SHH is the only member of the HH family that continues to be expressed in the adult brain (Traiffort et al, 2010). Under normal conditions, neurons appear to be the main SHH-secreting cell type (as opposed to SHH-responding cells, which are primarily of glial nature) (Garcia et al, 2010;Sirko et al, 2013;Traiffort et al, 1999). Following injury, however, SHH expression has been reported in reactive astrocytes (Amankulor et al, 2009;Sirko et al, 2013).…”

Section: Sources Of Shh In the Cnsmentioning

confidence: 99%

“…Under normal conditions, neurons appear to be the main SHH-secreting cell type (as opposed to SHH-responding cells, which are primarily of glial nature) (Garcia et al, 2010;Sirko et al, 2013;Traiffort et al, 1999). Following injury, however, SHH expression has been reported in reactive astrocytes (Amankulor et al, 2009;Sirko et al, 2013). In situ hybridization and genetic fate-mapping techniques to detect Shh expression have helped identify neurons in the medial and ventral septum of the adult forebrain as a possible ligand source for the SVZ (Fig.…”

Section: Sources Of Shh In the Cnsmentioning

confidence: 99%

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Roles for Hedgehog signaling in adult organ homeostasis and repair

2014

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The hedgehog (HH) pathway is well known for its mitogenic and morphogenic functions during development, and HH signaling continues in discrete populations of cells within many adult mammalian tissues. Growing evidence indicates that HH regulates diverse quiescent stem cell populations, but the exact roles that HH signaling plays in adult organ homeostasis and regeneration remain poorly understood. Here, we review recently identified functions of HH in modulating the behavior of tissue-specific adult stem and progenitor cells during homeostasis, regeneration and disease. We conclude that HH signaling is a key factor in the regulation of adult tissue homeostasis and repair, acting via multiple different routes to regulate distinct cellular outcomes, including maintenance of plasticity, in a context-dependent manner.

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Section: Fig 1 Mechanism Of Canonical Hh Signal Transduction In Vermentioning

confidence: 99%

Section: Fig 1 Mechanism Of Canonical Hh Signal Transduction In Vermentioning

confidence: 99%

Section: Fig 1 Mechanism Of Canonical Hh Signal Transduction In Vermentioning

confidence: 99%

Section: Sources Of Shh In the Cnsmentioning

confidence: 99%

Section: Sources Of Shh In the Cnsmentioning

confidence: 99%

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Roles for Hedgehog signaling in adult organ homeostasis and repair

2014

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Prospects for engineering neurons from local neocortical cell populations as cell‐mediated therapy for neurological disorders

Bazarek

Peterson

2014

J of Comparative Neurology

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There is little cell replacement following neurological injury, limiting the regenerative response of the CNS. Progress in understanding the biology of neural stem cells has raised interest in using stem cells for replacing neurons lost to injury or to disease. Stem cell therapy may also have a role in rebuilding deficient neural circuitry underlying mood disorders, epilepsy, and pain modulation among others. In vitro expansion of stem cells with directed differentiation prior to transplantation is one approach to stem cell therapy. Emerging evidence suggests that it may be possible to directly convert in vivo endogenous neural cells to a neuronal fate, providing an alternative strategy for stem cell therapy to the CNS. This review assesses the evidence for engineering subtype-specific neuronal fate of endogenous neural cells in the cerebral cortex as a function of initial cell lineage, reactive response to injury, conversion factors, and environmental context. We conclude with a discussion of some of the challenges that need to be overcome to move this alternative in vivo engineered conversion process towards becoming a viable therapeutic option.

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Studying Human Neurological Disorders Using Induced Pluripotent Stem Cells: From 2D Monolayer to 3D Organoid and Blood Brain Barrier Models

Logan

Arzua

Canfield

et al. 2019

Comprehensive Physiology

145

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Neurological disorders have emerged as a predominant healthcare concern in recent years due to their severe consequences on quality of life and prevalence throughout the world. Understanding the underlying mechanisms of these diseases and the interactions between different brain cell types is essential for the development of new therapeutics. Induced pluripotent stem cells (iPSCs) are invaluable tools for neurological disease modeling, as they have unlimited self-renewal and differentiation capacity. Mounting evidence shows: 1) various brain cells can be generated from iPSCs in 2-dimensional (2D) monolayer cultures; 2) further advances in 3D culture systems have led to the differentiation of iPSCs into organoids with multiple brain cell types and specific brain regions. These 3D organoids have gained widespread attention as in vitro tools to recapitulate complex features of the brain, and 3) Complex interactions between iPSC-derived brain cell types can recapitulate physiological and pathological conditions of blood-brain barrier (BBB). As iPSCs can be generated from diverse patient populations, researchers have effectively applied 2D, 3D and BBB models to recapitulate genetically complex neurological disorders and reveal novel insights into molecular and genetic mechanisms of neurological disorders. In this review, we describe recent progress in the generation of 2D, 3D and BBB models from iPSCs and further discuss their limitations, advantages, and future ventures. This review also covers the current status of applications of 2D, 3D and BBB models in drug screening, precision medicine, and modeling a wide range of neurological diseases (e.g., neurodegenerative diseases, neurodevelopmental disorders, brain injury, and neuropsychiatric disorders).

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Reactive Glia in the Injured Brain Acquire Stem Cell Properties in Response to Sonic Hedgehog

Cited by 119 publications

References 0 publications

Roles for Hedgehog signaling in adult organ homeostasis and repair

Roles for Hedgehog signaling in adult organ homeostasis and repair

Prospects for engineering neurons from local neocortical cell populations as cell‐mediated therapy for neurological disorders

Studying Human Neurological Disorders Using Induced Pluripotent Stem Cells: From 2D Monolayer to 3D Organoid and Blood Brain Barrier Models

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