LIF receptor signaling modulates neural stem cell renewal

Pitman, Matthew C.; Emery, Ben; Binder, Michele D.; Wang, S.; Butzkueven, Helmut; Kilpatrick, Trevor J.

doi:10.1016/j.mcn.2004.07.004

Cited by 84 publications

(81 citation statements)

References 39 publications

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“…Our results are consistent with and expand on recent studies examining the in vitro effects of LIF on embryonic neurospheres (Pitman et al, 2004;Bonaguidi et al, 2005), in which LIF promotes secondary sphere formation. Although LIF induces a marker of astrocyte differentiation (GFAP), the morphology and phenotype of these LIF-treated cells is distinct from astrocytes generated in the presence of bone morphogenic proteins (BMPs), another gliogenic cytokine family (Bonaguidi et al, 2005).…”

Section: Discussionsupporting

confidence: 92%

“…In another example, the dose of EGF has been reported to differentially affect type C cell phenotype (Doetsch et al, 2002). Discrepancies also exist in vitro, because some reports indicate that CNTF or LIF do not affect neurosphere formation (Shimazaki et al, 2001;Gregg and Weiss, 2005), whereas others find that they do (Pitman et al, 2004; present study; our unpublished results). Nevertheless, CNTF exposure for the last 4 DIV increases secondary neurosphere formation (Shimazaki et al, 2001), similar to the effect of LIF (present study).…”

Section: Discussionmentioning

confidence: 50%

“…Endogenous LIFR signaling promotes the maintenance of embryonic and adult NSCs in vivo and in vitro (Shimazaki et al, 2001;Pitman et al, 2004), and intracerebroventricular injection of anti-CNTF antibodies decreases adult neurogenesis (Emsley and Hagg, 2003). We did not address the role of endogenous LIF in this study, but LIF expression is generally very low under physiological conditions.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, LIF is well known for promoting mouse embryonic stem (ES) cell selfrenewal (Williams et al, 1988) and the long-term growth of embryonic human NSCs in culture (Wright et al, 2003). Other reports indicate that LIF signaling supports the maintenance/ self-renewal of cultured mouse embryonic NSCs (Shimazaki et al, 2001;Pitman et al, 2004;Bonaguidi et al, 2005;Gregg and Weiss, 2005), possibly by activating Notch signaling (Chojnacki et al, 2003). However, little is known about the influence of LIF signaling on NSCs and neurogenesis in vivo: gp130 regulates cellcycle reentry of embryonic cortical progenitors (Hatta et al, 2002), and exogenous CNTF enhances neurogenesis in the adult brain (Emsley and Hagg, 2003;Kokoeva et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Leukemia Inhibitory Factor Promotes Neural Stem Cell Self-Renewal in the Adult Brain

Bauer¹,

Patterson²

2006

J. Neurosci.

208

164

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Although neural stem cells (NSCs) persist in various areas of the adult brain, their contribution to brain repair after injury is very limited. Treatment with exogenous growth factors can mitigate this limitation, suggesting that the brain environment is normally deficient in permissive cues and that it may be possible to stimulate the latent regenerative potential of endogenous progenitors with appropriate signals. We analyzed the effects of overexpressing the cytokine leukemia inhibitory factor (LIF) on adult neurogenesis in the normal brain. We found that LIF reduces neurogenesis in the olfactory bulb and subventricular zone by acting directly on NSCs. LIF appears to promote NSC self-renewal, preventing the emergence of more differentiated cell types. This ultimately leads to an expansion of the NSC pool. Our results have implications for the development of therapeutic strategies for brain repair and suggest that LIF may be useful, in combination with other factors, in promoting regeneration in the adult brain.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Leukemia Inhibitory Factor Promotes Neural Stem Cell Self-Renewal in the Adult Brain

Bauer¹,

Patterson²

2006

J. Neurosci.

208

164

View full text Add to dashboard Cite

show abstract

“…Leukemia inhibitory factor (LIF) has been shown to aid in the maintenance of neural stem cells, both in vivo and in vitro (Carpenter et al, 1999;Shimazaki et al, 2001;Pitman et al, 2004;Bonaguidi et al, 2005). In mice, LIF increases the proportion of GFAP + immature NPCs within days of administration (Bonaguidi et al, 2005), whereas the effects of LIF on human fetal NPC growth are not apparent until 50-60 days in culture (Carpenter et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

In vitro growth and differentiation of canine olfactory bulb-derived neural progenitor cells under variable culture conditions

Walton

Wolfe

2008

Journal of Neuroscience Methods

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The dog serves as a large animal model for multiple neurologic diseases that may potentially benefit from neural progenitor cell (NPC) transplantation. In the adult brain, multipotent NPCs reside in the subventricular zone and its rostral and caudal extensions into the olfactory bulb and hippocampus. The olfactory bulb represents a surgically accessible site for obtaining cells for autologous NPC transplantation. To model conditions that would occur for ex vivo gene therapy in the postnatal brain, NPCs were isolated from the canine olfactory bulb, expanded ex vivo under different culture conditions, and compared quantitatively for growth and immunophenotype. Under standard growth conditions, canine olfactory bulb-derived NPCs (OB-cNPCs) could be expanded nearly 500-fold in the time evaluated. Canine OB-cNPCs grown on poly-D-lysine (PDL) or on PDL-fibronectin had similar growth rates, whereas supplementation with leukemia inhibitory factor (LIF) resulted in significantly slower growth. However, when OB-cNPC cultures were grown on PDL-fibronectin or PDL supplemented with LIF, a greater proportion of cells with neuronal markers were generated upon differentiation.

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Oncostatin M regulates neural precursor activity in the adult brain

Beatus

Jhaveri

Walker

et al. 2011

Developmental Neurobiology

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The regulation of neural precursor cell (NPC) activity is the major determinant of the rate of neuronal production in neurogenic regions of the adult brain. Here, we show that Oncostatin M (Osm) and its receptor, OsmRβ, are both expressed in the subventricular zone (SVZ) and that in contradistinction to leukemia inhibitory factor and ciliary neutrophic factor, Osm directly inhibits the proliferation of adult NPCs as measured by a decreased level of neurosphere formation in vitro. Similarly, intraventricular infusion of Osm dramatically decreases the pool of NPCs in both the SVZ and the hippocampus. In keeping with the inhibitory action of Osm, we reveal that mice lacking OsmRβ have substantially more NPCs in the SVZ, the hippocampus and the olfactory bulb, demonstrating that endogenous Osm signaling is important for NPC homeostasis. Finally, we show that Osm can also inhibit clonal growth of glioblastoma-derived neurospheres, further supporting the close link between NPCs and tumor stem cells.

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LIF receptor signaling modulates neural stem cell renewal

Cited by 84 publications

References 39 publications

Leukemia Inhibitory Factor Promotes Neural Stem Cell Self-Renewal in the Adult Brain

Leukemia Inhibitory Factor Promotes Neural Stem Cell Self-Renewal in the Adult Brain

In vitro growth and differentiation of canine olfactory bulb-derived neural progenitor cells under variable culture conditions

Oncostatin M regulates neural precursor activity in the adult brain

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