Liver X receptors and oxysterols promote ventral midbrain neurogenesis in vivo and in human embryonic stem cells.
Cell Stem Cell
; 5(4): 409-19, 2009 Oct 02.
Article
en En
| MEDLINE
| ID: mdl-19796621
ABSTRACT
Control over progenitor proliferation and neurogenesis remains a key challenge for stem cell neurobiology and a prerequisite for successful stem cell replacement therapies for neurodegenerative diseases like Parkinson's disease (PD). Here, we examined the function of two nuclear receptors, liver X receptors (Lxralpha and beta) and their ligands, oxysterols, as regulators of cell division, ventral midbrain (VM) neurogenesis, and dopaminergic (DA) neuron development. Deletion of Lxrs reduced cell cycle progression and VM neurogenesis, resulting in decreased DA neurons at birth. Activation of Lxrs with oxysterol ligands increased the number of DA neurons in mouse embryonic stem cells (ESCs) and in wild-type but not Lxralphabeta(-/-) VM progenitor cultures. Likewise, oxysterol treatment of human ESCs (hESCs) during DA differentiation increased neurogenesis and the number of mature DA neurons, while reducing proliferating progenitors. Thus, Lxr ligands may improve current hESC replacement strategies for PD by selectively augmenting the generation of DA neurons.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Mesencéfalo
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Colesterol
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Células Madre Embrionarias
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Neurogénesis
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Receptores Nucleares Huérfanos
Límite:
Animals
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Humans
Idioma:
En
Revista:
Cell Stem Cell
Año:
2009
Tipo del documento:
Article
País de afiliación:
Suecia