Open AccessPhenazopyridine induces and synchronizes neuronal differentiation of embryonic stem cells
Author(s) -
Suter David M.,
PreynatSeauve Olivier,
Tirefort Diderik,
Feki Anis,
Krause KarlHeinz
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00660.x
Subject(s) - cellular differentiation , embryonic stem cell , microbiology and biotechnology , neural stem cell , stem cell , biology , directed differentiation , neurosphere , p19 cell , cell culture , neuroscience , adult stem cell , induced pluripotent stem cell , biochemistry , gene , genetics
Embryonic stem (ES) cells are powerful tools to understand mechanisms of neuronal differentiation and to engineer neurons for in vitro studies and cell therapy. We developed a screening approach to identify small organic molecules driving neuronal differentiation of ES cells. For this purpose, we used a lentivector carrying a dual luciferase reporter system to engineer an ES cell line which allowed us to screen for small organic molecules enhancing neuronal differentiation. One of them, phenazopyridine, was further analysed in human ES cells. Phenazopyridine: ( i ) enhanced neuronal differentiation, ( ii ) increased cell survival, ( iii ) decreased the amount of non‐neuronal and undifferentiated cells and ( iv ) synchronized the cellular differentiation state. Phenazopyridine allowed the development of a differentiation protocol compatible with the generation of clinical grade neural precursors, which were able differentiate into different neuronal subtypes, astrocytes and oligodendrocytes. In summary, we describe a powerful approach to identify small molecules directing stem cell differentiation. This led to the establishment of a new application for an old drug and the development of a novel clinical grade protocol for neuronal differentiation of ES cells.