Inducible expression of noggin selectively expands neural progenitors in the adult SVZ

Morell, María; Tsan, Yao chang; O’Shea, K. Sue

doi:10.1016/j.scr.2014.11.001

Cited by 26 publications

(16 citation statements)

References 88 publications

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“…BMP receptor activation inhibits proliferation and suppresses SVZ neurogenesis while promoting gliogenesis (Lim et al, ). Several groups have further shown that BMP suppresses oligodendrogenesis while promoting astrogenesis (Gomes, Mehler, & Kessler, ; Mabie et al, ; Morell, Tsan, & O'Shea, ). Other data suggest BMP suppresses the oligodendrocytic fate but has a permissive effect on olfactory bulb neurogenesis (Colak et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Galectin‐3 modulates postnatal subventricular zone gliogenesis

Al‐Dalahmah

Soares

Nicholson

et al. 2019

Glia

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Postnatal subventricular zone (SVZ) neural stem cells generate forebrain glia, namely astrocytes and oligodendrocytes. The cues necessary for this process are unclear, despite this phase of brain development being pivotal in forebrain gliogenesis. Galectin‐3 (Gal‐3) is increased in multiple brain pathologies and thereby regulates astrocyte proliferation and inflammation in injury. To study the function of Gal‐3 in inflammation and gliogenesis, we carried out functional studies in mouse. We overexpressed Gal‐3 with electroporation and using immunohistochemistry surprisingly found no inflammation in the healthy postnatal SVZ. This allowed investigation of inflammation‐independent effects of Gal‐3 on gliogenesis. Loss of Gal‐3 function via knockdown or conditional knockout reduced gliogenesis, whereas Gal‐3 overexpression increased it. Gal‐3 overexpression also increased the percentage of striatal astrocytes generated by the SVZ but decreased the percentage of oligodendrocytes. These novel findings were further elaborated with multiple analyses demonstrating that Gal‐3 binds to the bone morphogenetic protein receptor one alpha (BMPR1α) and increases bone morphogenetic protein (BMP) signaling. Conditional knockout of BMPR1α abolished the effect of Gal‐3 overexpression on gliogenesis. Gain‐of‐function of Gal‐3 is relevant in pathological conditions involving the human forebrain, which is particularly vulnerable to hypoxia/ischemia during perinatal gliogenesis. Hypoxic/ischemic injury induces astrogliosis, inflammation and cell death. We show that Gal‐3 immunoreactivity was increased in the perinatal human SVZ and striatum after hypoxia/ischemia. Our findings thus show a novel inflammation‐independent function for Gal‐3; it is necessary for gliogenesis and when increased in expression can induce astrogenesis via BMP signaling.

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Section: Introductionmentioning

confidence: 99%

“…BMP receptor activation inhibits proliferation and suppresses SVZ neurogenesis while promoting gliogenesis (Lim et al, 2000). Several groups have further shown that BMP suppresses oligodendrogenesis while promoting astrogenesis (Gomes, Mehler, & Kessler, 2003;Mabie et al, 1997;Morell, Tsan, & O'Shea, 2014).…”

Section: Introductionmentioning

confidence: 99%

Galectin‐3 modulates postnatal subventricular zone gliogenesis

Al‐Dalahmah

Soares

Nicholson

et al. 2019

Glia

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“…The most commonly used approaches to induce differentiation of MSCs into neuron-like cell include (1) antioxidant agents such as mercaptoethanol, dimethylsulfoxide (DMSO), and beta hydroxy acid (BHA); (2) neurotropic factors such as retinoic acid (RA), nerve growth factor (NGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), brain derived neurotropic factor (BDNF); (3) Chinese herbs and their effective components such as astragalus glycosides, berberine, tanshinone, lycium barbarum polysaccharide, acanthopanax; (4) cultural method; and (5) gene transfection: transfection of specific genes such as Noggin [5] and Notch into hUC-MSCs to get neuron-like cell. However, these differentiation approaches are of low efficiency.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Induces Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into Neuron-Like Cells

Guo

Wang

et al. 2017

Stem Cells International

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Objective. Human umbilical cord mesenchymal stem cells (hUC-MSCs) potentially differentiate to various types of cells including neuron-like cells. The natural polyphenol resveratrol benefits patients with many diseases including ischemic brain injury. We hypothesize that resveratrol induces differentiation of hUC-MSCs into neuron-like cells. Methods. Flow cytometry was used to determine the surface antigens in different stage of hUC-MSCs (P2, P5, and P10). Nestin, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP) were detected by immunocytochemistry, Western blotting, and real time RT-PCT. The cultured hUC-MSCs were treated with resveratrol at different concentrations (0, 7.5, 15.0, and 30.0 mg/L). Nestin, GFAP, and NSE protein and mRNA were measured at posttreatment time points of 2 h, 4 h, 6 h, 12 h, and 24 h. Results. Neuron-like cells were found in hUC-MSCs treated by resveratrol at concentrations of 15.0 and 30.0 mg/L, but not in hUC-MSCs treated with vehicle and 7.5 mg/L resveratrol. Furthermore, immunocytochemical staining revealed that nestin and NSE immunoreactivities were positive in resveratrol-treated hUC-MSCs at concentrations of 15.0 and 30.0 mg/L. Resveratrol treatment significantly increased nestin and NSE protein and mRNA levels 4 h after the treatment. However, resveratrol treatment did not change GFAP immunoreactivities and protein and mRNA expression levels in cultured hUC-MSCs. Conclusions. Taken together, resveratrol treatment induces a differentiation of hUC-MSCs into neuron-like cells at relatively high concentrations.

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“…Here, we focused on bone morphogenetic proteins (BMPs). BMPs are expressed locally within the SVZ, where they have been shown to promote production of astrocytes at the expense of neurons and oligodendrocytes (Lim et al, 2000 ; Morell et al, 2014 ). Inhibition of endogenous BMP signaling modulates neurogenesis in both the SVZ and dentate gyrus niches, although there is conflicting data that likely reflects unresolved stage-specific effects on the neurogenic lineage and differences between niches (Lim et al, 2000 ; Bonaguidi et al, 2008 ; Colak et al, 2008 ; Gobeske et al, 2009 ; Mira et al, 2010 ; Guo et al, 2011 ; Bond et al, 2012 , 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Bone morphogenetic protein dominantly suppresses epidermal growth factor-induced proliferative expansion of adult forebrain neural precursors

et al. 2015

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A single asymmetric division by an adult neural stem cell (NSC) ultimately generates dozens of differentiated progeny, a feat made possible by the proliferative expansion of transit-amplifying progenitor cells (TAPs). Although NSC activation and TAP expansion is determined by pro- and anti-proliferative signals found within the niche, remarkably little is known about how these cells integrate simultaneous conflicting signals. We investigated this question focusing on the subventricular zone (SVZ) niche of the adult murine forebrain. Using primary cultures of SVZ cells, we demonstrate that Epidermal Growth Factor (EGF) and Bone Morphogenetic Protein (BMP)-2 are particularly powerful pro- and anti-proliferative factors for SVZ-derived neural precursors. Dose-response experiments showed that when simultaneously exposed to both signals, BMP dominantly suppressed EGF-induced proliferation; moreover, this dominance extended to all parameters of neural precursor behavior tested, including inhibition of proliferation, modulation of cell cycle, promotion of differentiation, and increase of cell death. BMP's anti-proliferative effect did not involve inhibition of mTORC1 or ERK signaling, key mediators of EGF-induced proliferation, and had distinct stage-specific consequences, promoting TAP differentiation but NSC quiescence. In line with these in vitro data, in vivo experiments showed that exogenous BMP limits EGF-induced proliferation of TAPs while inhibition of BMP-SMAD signaling promotes activation of quiescent NSCs. These findings clarify the stage-specific effects of BMPs on SVZ neural precursors, and support a hierarchical model in which the anti-proliferative effects of BMP dominate over EGF proliferation signaling to constitutively drive TAP differentiation and NSC quiescence.

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Inducible expression of noggin selectively expands neural progenitors in the adult SVZ

Cited by 26 publications

References 88 publications

Galectin‐3 modulates postnatal subventricular zone gliogenesis

Galectin‐3 modulates postnatal subventricular zone gliogenesis

Resveratrol Induces Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into Neuron-Like Cells

Bone morphogenetic protein dominantly suppresses epidermal growth factor-induced proliferative expansion of adult forebrain neural precursors

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