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Role of ERb in neural differentiation of mouse embryonic stem cells

ABSTRACT: Global gene expression profile of midbrain neural differentiation of mESCs from WT and ERb knockout mice, with or without the selective ERb agonist LY3201 (0.5 nM). Estrogen receptor beta (ERβ) is highly expressed in the fetal brain and is essential for proper corticogenesis during development. Nevertheless, the transcriptional signatures regulated by ERβ during defined neural differentiation stages have not been investigated. In the present study we used mouse embryonic stem cells (mESCs) from wildtype (WT) and ERβ knockout (BERKO) mice to derive neural precursor cells (NPCs) and further differentiated these towards defined midbrain neural fates. This allowed us to systematically investigate transcriptionally active determinants during stages of midbrain neurogenesis. We found that ERβ is important during early neural development in regulating proliferation and maintaining the stem cell pool of neuroepithelial and midbrain stem cells. Detailed gene profiling analysis revealed that loss of ERβ perturbs normal neurogenesis by affecting the expression of factors involved in cell adhesion, axon guidance, and signaling of Notch, Wnt, glutamate- and GABA receptors. Among these we identified several factors that are crucial for dopaminergic neuron development and maintenance, as well as the promotion of oligodendrocyte differentiation. We also demonstrate that these effects are largely independent of ligand activated ERβ. Our data identifies ERβ as an important component in midbrain neurogenesis, where its disruption results in premature depletion of the neural stem cell pool in favor of oligodendrogliogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE103312 | GEO | 2017/10/09

SECONDARY ACCESSION(S): PRJNA401675

REPOSITORIES: GEO

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