Liver X Receptors and Oxysterols Promote Ventral Midbrain Neurogenesis In Vivo and in Human Embryonic Stem Cells

Paola Sacchetti, Kyle M. Sousa, Anita C. Hall, Isabel Liste, Knut R. Steffensen, Spyridon Theofilopoulos, Clare L. Parish, Carin Hazenberg, Lars Ährlund Richter, Outti Hovatta, Jan Åke Gustafsson, Ernest Arenas

Research output: Contribution to journalArticle

101 Scopus citations

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 (Lxrα and β) 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 Lxrαβ-/- 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.

Original languageEnglish (US)
Pages (from-to)409-419
Number of pages11
JournalCell Stem Cell
Volume5
Issue number4
DOIs
StatePublished - Oct 2 2009

Keywords

  • HUMDISEASE
  • STEMCELL

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Fingerprint Dive into the research topics of 'Liver X Receptors and Oxysterols Promote Ventral Midbrain Neurogenesis In Vivo and in Human Embryonic Stem Cells'. Together they form a unique fingerprint.

Cite this