Hypothalamic regulation of regionally distinct adult neural stem cells and neurogenesis

Science ◽  
2017 ◽  
Vol 356 (6345) ◽  
pp. 1383-1386 ◽  
Author(s):  
Alex Paul ◽  
Zayna Chaker ◽  
Fiona Doetsch
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Adult Mouse ◽  
Brain Area ◽  
Regional Identity ◽  
Mammalian Brain ◽  
Granule Neurons ◽  
Environmental Signals ◽  
Hypothalamic Regulation ◽  
Adult Mammalian Brain

Neural stem cells (NSCs) in specialized niches in the adult mammalian brain generate neurons throughout life. NSCs in the adult mouse ventricular-subventricular zone (V-SVZ) exhibit a regional identity and, depending on their location, generate distinct olfactory bulb interneuron subtypes. Here, we show that the hypothalamus, a brain area regulating physiological states, provides long-range regionalized input to the V-SVZ niche and can regulate specific NSC subpopulations. Hypothalamic proopiomelanocortin neurons selectively innervate the anterior ventral V-SVZ and promote the proliferation of Nkx2.1+ NSCs and the generation of deep granule neurons. Accordingly, hunger and satiety regulate adult neurogenesis by modulating the activity of this hypothalamic–V-SVZ connection. Our findings reveal that neural circuitry, via mosaic innervation of the V-SVZ, can recruit distinct NSC pools, allowing on-demand neurogenesis in response to physiology and environmental signals.

scholarly journals Composition and Organization of the SCZ: A Large Germinal Layer Containing Neural Stem Cells in the Adult Mammalian Brain

2006 ◽  
Vol 16 (suppl_1) ◽  
pp. i103-i111 ◽  
Author(s):  
B. Seri ◽  
D.G. Herrera ◽  
A. Gritti ◽  
S. Ferron ◽  
L. Collado ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Mammalian Brain ◽  
Germinal Layer ◽  
Adult Mammalian Brain

scholarly journals Primitive Neural Stem Cells in the Adult Mammalian Brain Give Rise to GFAP-Expressing Neural Stem Cells

2014 ◽  
Vol 2 (6) ◽  
pp. 810-824 ◽  
Author(s):  
Nadia Sachewsky ◽  
Rachel Leeder ◽  
Wenjun Xu ◽  
Keeley L. Rose ◽  
Fenggang Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Mammalian Brain ◽  
Adult Mammalian Brain

scholarly journals Transcriptomic analysis of loss of Gli1 in neural stem cells responding to demyelination in the mouse brain

2021 ◽  
Author(s):  
Jayshree Samanta ◽  
James L. Salzer
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Molecular Mechanisms ◽  
Control Diet ◽  
Transcriptomic Analysis ◽  
Demyelinating Diseases ◽  
Mammalian Brain ◽  
Adult Mice ◽  
Pharmacologic Inhibition ◽  
Adult Mammalian Brain

ABSTRACTIn the adult mammalian brain, Gli1 expressing neural stem cells reside in the subventricular zone and their progeny are recruited to sites of demyelination in the white matter where they regenerate oligodendrocytes, the myelin forming cells. Remarkably, genetic loss or pharmacologic inhibition of Gli1 enhances the efficacy of remyelination by these neural stem cells. To understand the molecular mechanisms involved, we performed a transcriptomic analysis of this Gli1-pool of neural stem cells. We compared murine NSCs with either intact or deficient Gli1 expression from adult mice on a control diet or on a cuprizone diet to induce widespread demyelination. These data will be a valuable resource for identifying therapeutic targets for enhancing remyelination in demyelinating diseases like multiple sclerosis.

Neural stem cell lineages are regionally specified, but not committed, within distinct compartments of the developing brain

Development ◽  
2002 ◽  
Vol 129 (1) ◽  
pp. 233-244 ◽  
Author(s):  
Seiji Hitoshi ◽  
Vincent Tropepe ◽  
Marc Ekker ◽  
Derek van der Kooy
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Regional Identity ◽  
Developing Brain ◽  
Mammalian Brain ◽  
Ganglionic Eminence ◽  
Neural Lineage

Regional patterning in the developing mammalian brain is partially regulated by restricted gene expression patterns within the germinal zone, which is composed of stem cells and their progenitor cell progeny. Whether or not neural stem cells, which are considered at the top of the neural lineage hierarchy, are regionally specified remains unknown. Here we show that the cardinal properties of neural stem cells (self-renewal and multipotentiality) are conserved among embryonic cortex, ganglionic eminence and midbrain/hindbrain, but that these different stem cells express separate molecular markers of regional identity in vitro, even after passaging. Neural stem cell progeny derived from ganglionic eminence but not from other regions are specified to respond to local environmental cues to migrate ventrolaterally, when initially deposited on the germinal layer of ganglionic eminence in organotypic slice cultures. Cues exclusively from the ventral forebrain in a 5 day co-culture paradigm could induce both early onset and late onset marker gene expression of regional identity in neural stem cell colonies derived from both the dorsal and ventral forebrain as well as from the midbrain/hindbrain. Thus, neural stem cells and their progeny are regionally specified in the developing brain, but this regional identity can be altered by local inductive cues.

Genetically Perpetuated Human Neural Stem Cells Engraft and Differentiate into the Adult Mammalian Brain

2000 ◽  
Vol 16 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Francisco Javier Rubio ◽  
Carlos Bueno ◽  
Ana Villa ◽  
Beatriz Navarro ◽  
Alberto Martı́nez-Serrano
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Mammalian Brain ◽  
Human Neural Stem Cells ◽  
Adult Mammalian Brain

scholarly journals Overexpression of cdk4 and cyclinD1 triggers greater expansion of neural stem cells in the adult mouse brain

2011 ◽  
Vol 208 (5) ◽  
pp. 937-948 ◽  
Author(s):  
Benedetta Artegiani ◽  
Dirk Lindemann ◽  
Federico Calegari
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Adult Neurogenesis ◽  
Adult Mouse ◽  
Physiological Role ◽  
Mammalian Brain ◽  
Temporal Control ◽  
Somatic Stem Cells

Neural stem cells (NSCs) in the adult mammalian brain generate neurons and glia throughout life. However, the physiological role of adult neurogenesis and the use of NSCs for therapy are highly controversial. One factor hampering the study and manipulation of neurogenesis is that NSCs, like most adult somatic stem cells, are difficult to expand and their switch to differentiation is hard to control. In this study, we show that acute overexpression of the cdk4 (cyclin-dependent kinase 4)–cyclinD1 complex in the adult mouse hippocampus cell-autonomously increases the expansion of neural stem and progenitor cells while inhibiting neurogenesis. Importantly, we developed a system that allows the temporal control of cdk4–cyclinD1 overexpression, which can be used to increase the number of neurons generated from the pool of manipulated precursor cells. Beside providing a proof of principle that expansion versus differentiation of somatic stem cells can be controlled in vivo, our study describes, to the best of our knowledge, the first acute and inducible temporal control of neurogenesis in the mammalian brain, which may be critical for identifying the role of adult neurogenesis, using NSCs for therapy, and, perhaps, extending our findings to other adult somatic stem cells.

scholarly journals Gpnmb inhibits oligodendrocyte differentiation of adult neural stem cells by amplifying TGFβ1 signaling

2021 ◽  
Author(s):  
Daniel Z Radecki ◽  
Albert R Wang ◽  
Abigail S Johnson ◽  
Christian A Overman ◽  
Madison M Thatcher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Signaling Pathway ◽  
Subventricular Zone ◽  
Mammalian Brain ◽  
Receptor Subunit ◽  
Oligodendrocyte Differentiation ◽  
Feed Forward Loop ◽  
Adult Mammalian Brain ◽  
Sustained Activation

Gli1 expressing neural stem cells, in the subventricular zone of the adult mammalian brain, respond to demyelination injury by differentiating into oligodendrocytes. We have identified Gpnmb as a novel regulator of oligodendrogenesis in Gli1 neural stem cells, whose expression is induced by TGFβ1 signaling via Gli1, in response to a demyelinating injury. Upregulation of Gpnmb further activates the TGFβ1 pathway by increasing the expression of the TGFβ1 binding receptor subunit, TGFβR2. Thus the TGFβ1→Gli1→Gpnmb→TGFβR2 signaling pathway forms a feed forward loop for sustained activation of TGFβ1 signaling in Gli1 neural stem cells, resulting in inhibition of their differentiation into mature oligodendrocytes following demyelination.

scholarly journals Transcriptomic analysis of loss of Gli1 in neural stem cells responding to demyelination in the mouse brain

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Jayshree Samanta ◽  
Hernandez Moura Silva ◽  
Juan J. Lafaille ◽  
James L. Salzer
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Molecular Mechanisms ◽  
Control Diet ◽  
Transcriptomic Analysis ◽  
Demyelinating Diseases ◽  
Mammalian Brain ◽  
Adult Mice ◽  
Pharmacologic Inhibition ◽  
Adult Mammalian Brain

AbstractIn the adult mammalian brain, Gli1 expressing neural stem cells reside in the subventricular zone and their progeny are recruited to sites of demyelination in the white matter where they generate new oligodendrocytes, the myelin forming cells. Remarkably, genetic loss or pharmacologic inhibition of Gli1 enhances the efficacy of remyelination by these neural stem cells. To understand the molecular mechanisms involved, we performed a transcriptomic analysis of this Gli1-pool of neural stem cells. We compared murine NSCs with either intact or deficient Gli1 expression from adult mice on a control diet or on a cuprizone diet which induces widespread demyelination. These data will be a valuable resource for identifying therapeutic targets for enhancing remyelination in demyelinating diseases like multiple sclerosis.

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