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Dev Neurobiol. 2019 Jun;79(6):559-577. doi: 10.1002/dneu.22703. Epub 2019 Jun 29.

Induction of Tyrosine Hydroxylase Gene Expression in Embryonal Carcinoma Stem Cells Using a Natural Tissue-Specific Inducer.

Author information

1
Department of Biology, Faculty of Sciences, University of Isfahan, Hezarjerib Avenue, Isfahan, 8174673441, Iran.
2
School of Life Science (LifeNet), Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, 79106, Germany.
3
Center for Biological Systems Analysis (ZBSA), University Medical Center Freiburg, Freiburg, Germany.

Abstract

A large number of studies have focused on the generation of dopaminergic neurons from pluripotent cells. Differentiation of stem cells into distinct cell types is influenced by tissue-specific microenvironment. Since, central nervous system undergoes further development during postnatal life, in the present study neonatal rat brain tissue extract (NRBE) was applied to direct the differentiation of embryonal carcinoma stem cell line, P19 into dopaminergic (DA) phenotypes. Additionally, a neuroprotective drug, deprenyl was used alone or in combination with the extract. Results from morphological, immunofluorescence, and qPCR analyses showed that during a period of one to three weeks, a large percentage of stem cells were differentiated into neural cells. The results also indicated the greater effect of NRBE on the differentiation of the cells into tyrosine hydroxylase-expressing cells. MS analysis of NRBE showed the enrichment of gene ontology terms related to cell differentiation and neurogenesis. Network analysis of the studied genes and some DA markers resulted in the suggestion of potential regulatory candidates such as AVP, ACHE, LHFPL5, and DLK1 genes. In conclusion, NRBE as a natural native inducer was apparently able to simulate the brain microenvironment and support neural differentiation of P19 cells.

KEYWORDS:

brain development; dopaminergic neurons; embryonal carcinoma stem cells; natural inducers; neural differentiation; tyrosine hydroxylase

PMID:
31177638
DOI:
10.1002/dneu.22703

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