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Updated: Feb 18, 2026
Differentiation and Characterization of Neural Progenitors and Neurons from Mouse Embryonic Stem Cells
Published on: May 15, 2020
Role of estrogen receptor beta in neural differentiation of mouse embryonic stem cells
Mukesh K Varshney1, José Inzunza1, Diana Lupu1,2,3
1Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, Sweden.
Abstract:
The ability to propagate mature cells and tissue from pluripotent stem cells offers enormous promise for treating many diseases, including neurodegenerative diseases. Before such cells can be used successfully in neurodegenerative diseases without causing unwanted cell growth and migration, genes regulating growth and migration of neural stem cells need to be well characterized. Estrogen receptor beta (ERβ) is essential for migration of neurons and glial cells in the developing mouse brain. To examine whether ERβ influences differentiation of mouse embryonic stem cells (mESC) into neural lineages, we compared control and ERβ knockout (BERKO) mESCs at defined stages of neural development and examined the effects of an ERβ-selective ligand (LY3201) with a combination of global and targeted gene-expression profiling and the expression of key pluripotency markers. We found that ERβ was induced in embryoid bodies (EBs) and neural precursor cells (NPCs) during development. Proliferation was higher in BERKO NPCs and was inhibited by LY3201. Neurogenesis was reduced in BERKO ES cells, and oligodendrogliogenesis was enhanced. BERKO EBs expressed higher levels of key ectodermal and neural progenitor markers and lower levels of markers for mesoderm and endoderm lineages. ERβ-regulated factors are involved in cell adhesion, axon guidance, and signaling of Notch and GABA receptor pathways, as well as factors important for the differentiation of neuronal precursors into dopaminergic neurons (Engrailed 1) and for the oligodendrocyte fate acquisition (Olig2). Our data suggest that ERβ is an important component for differentiation into midbrain neurons as well as for preventing precocious oligodendrogliogenesis.
Insights
Estrogen receptor beta (ERβ) regulates neural stem cell differentiation. Its absence enhances oligodendrocyte development but reduces midbrain neuron formation, suggesting ERβ
Area of Science:
- Stem cell biology
- Neuroscience
- Endocrinology
Background:
- Pluripotent stem cells hold promise for treating neurodegenerative diseases.
- Understanding neural stem cell growth and migration is crucial for safe therapeutic applications.
- Estrogen receptor beta (ERβ) plays a role in neural cell migration during brain development.
Purpose of the Study:
- To investigate the influence of ERβ on the differentiation of mouse embryonic stem cells (mESCs) into neural lineages.
- To compare the neural differentiation of control mESCs with ERβ knockout (BERKO) mESCs.
- To assess the impact of an ERβ-selective ligand (LY3201) on neural differentiation.
Main Methods:
- Utilized control and BERKO mESCs at defined neural development stages.
- Employed global and targeted gene-expression profiling.
- Analyzed pluripotency markers and key lineage markers.
Main Results:
- ERβ expression increased during embryoid body (EB) and neural precursor cell (NPC) development.
- BERKO NPCs showed higher proliferation, inhibited by LY3201.
- Neurogenesis was reduced, while oligodendrogliogenesis was enhanced in BERKO cells.
- BERKO EBs displayed increased ectodermal/neural progenitor markers and decreased mesoderm/endoderm markers.
- ERβ influences cell adhesion, axon guidance, Notch, GABA pathways, and specific neuronal/glial differentiation factors (Engrailed 1, Olig2).
Conclusions:
- ERβ is essential for proper neural stem cell differentiation.
- ERβ regulates the balance between neurogenesis and oligodendrogliogenesis.
- ERβ is critical for midbrain dopaminergic neuron differentiation and preventing premature oligodendrocyte development.
