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Role of COUP‐TFI during retinoic acid‐induced differentiation of P19 cells to endodermal cells
Author(s) -
Pickens Brandy S.,
Teets Bryan W.,
Soprano Kenneth J.,
Soprano Dianne Robert
Publication year - 2013
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24228
Subject(s) - p19 cell , retinoic acid , microbiology and biotechnology , gene silencing , cellular differentiation , biology , cell culture , gene , genetics , adult stem cell
Retinoic acid (RA) is a positive regulator of P19 cell differentiation. Silencing of pre‐B cell leukemia transcription factors (PBXs) expression in P19 cells (AS cells) results in a failure of these cells to differentiate to endodermal cells upon RA treatment. Chicken Ovalbumin Upstream Promoter Transcription Factor I (COUP‐TFI) is an orphan member of the steroid‐thyroid hormone superfamily. RA treatment of wild type P19 cells results in a dramatic increase in the expression of COUP‐TFI; however, COUP‐TFI mRNA levels fail to be elevated upon RA treatment of AS cells indicating that PBX expression is required for elevation in COUP‐TFI expression. To study the role of COUP‐TFI during RA‐dependent differentiation of P19 cells, AS cells that inducibly express various levels of COUP‐TFI were prepared. Exogenous expression of COUP‐TFI in AS cells, in a dose‐dependent fashion, leads to growth inhibition, modest cell cycle disruption, and early apoptosis. Furthermore, AS cells can overcome the blockage in RA‐dependent differentiation to endodermal cells when either pharmacological levels of COUP‐TFI are expressed or a combination of both the expression of physiological levels of COUP‐TFI and RA treatment. Additionally, the mRNA level of several pluripotency associated genes including OCT‐4, DAX‐1, and SF‐1 in the COUP‐TFI expressing AS cells are reduced. Moreover, analysis of the expression of primary RA response genes indicates that COUP‐TFI is involved in the regulatory modulation of the expression of at least two genes, CYP26A1 and HoxA1. These studies demonstrate that COUP‐TFI functions as a physiologically relevant regulator during RA‐mediated endodermal differentiation of P19 cells. J. Cell. Physiol. 228: 791–800, 2013. © 2012 Wiley Periodicals, Inc.