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

doi:10.1016/j.stem.2009.08.019

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 journal › Article

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 language	English (US)
Pages (from-to)	409-419
Number of pages	11
Journal	Cell Stem Cell
Volume	5
Issue number	4
DOIs	https://doi.org/10.1016/j.stem.2009.08.019
State	Published - Oct 2 2009

Keywords

HUMDISEASE
STEMCELL

ASJC Scopus subject areas

Cell Biology
Molecular Medicine
Genetics

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Sacchetti, P., Sousa, K. M., Hall, A. C., Liste, I., Steffensen, K. R., Theofilopoulos, S., Parish, C. L., Hazenberg, C., Richter, L. Ä., Hovatta, O., Gustafsson, J. Å., & Arenas, E. (2009). Liver X Receptors and Oxysterols Promote Ventral Midbrain Neurogenesis In Vivo and in Human Embryonic Stem Cells. Cell Stem Cell, 5(4), 409-419. https://doi.org/10.1016/j.stem.2009.08.019

Liver X Receptors and Oxysterols Promote Ventral Midbrain Neurogenesis In Vivo and in Human Embryonic Stem Cells. / Sacchetti, Paola; Sousa, Kyle M.; Hall, Anita C.; Liste, Isabel; Steffensen, Knut R.; Theofilopoulos, Spyridon; Parish, Clare L.; Hazenberg, Carin; Richter, Lars Ährlund; Hovatta, Outti; Gustafsson, Jan Åke; Arenas, Ernest.

In: Cell Stem Cell, Vol. 5, No. 4, 02.10.2009, p. 409-419.

Research output: Contribution to journal › Article

Sacchetti, Paola ; Sousa, Kyle M. ; Hall, Anita C. ; Liste, Isabel ; Steffensen, Knut R. ; Theofilopoulos, Spyridon ; Parish, Clare L. ; Hazenberg, Carin ; Richter, Lars Ährlund ; Hovatta, Outti ; Gustafsson, Jan Åke ; Arenas, Ernest. / Liver X Receptors and Oxysterols Promote Ventral Midbrain Neurogenesis In Vivo and in Human Embryonic Stem Cells. In: Cell Stem Cell. 2009 ; Vol. 5, No. 4. pp. 409-419.

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