© 1995 American Heart Association, Inc.
Articles |
A Retinoic Acid–Induced Clonal Cell Line Derived From Multipotential P19 Embryonal Carcinoma Cells Expresses Smooth Muscle Characteristics
From the University of Virginia School of Medicine, Department of Molecular Physiology and Biological Physics, Charlottesville, and the Department of Biochemistry and Molecular Biology, M.D. Anderson Cancer Center (E.N.O.), Houston, Tex.
Correspondence to Gary K. Owens, PhD, Department of Molecular Physiology and Biological Physics, Box 449 Jordan Hall, University of Virginia, Charlottesville, VA.
Abstract Despite intense interest in understanding the
differentiation of vascular smooth muscle, very little is known about
the cellular and molecular mechanisms that control differentiation of
this cell type. Progress in this field has been hampered by the lack of
an inducible in vitro system for study of the early steps of smooth
muscle differentiation. In this study, we describe a model system in
which multipotential mouse P19 embryonal carcinoma cells (P19s) can be
induced to express multiple characteristics of differentiated smooth
muscle. Treatment of P19s with retinoic acid was associated with
profound changes in cell morphology and with the appearance at high
frequency of smooth muscle 
-actin–positive cells that were absent
or present at extremely low frequency in parental P19s. A clonal
line derived from retinoic acid–treated P19s (9E11G) stably expressed
multiple characteristics of differentiated smooth muscle, including
smooth muscle–specific isoforms of -actin and myosin heavy chain,
as well as functional responses to the contractile agonists
phenylephrine, angiotensin II, ATP, bradykinin, histamine,
platelet-derived growth factor (PDGF)-AA, and PDGF-BB.
Additionally, 9E11G cells expressed transcripts for
MHox, a muscle homeobox gene expressed in smooth,
cardiac, and skeletal muscles, but not the skeletal muscle–specific
regulatory factors, MyoD and myogenin. Results demonstrate
that retinoic acid treatment of multipotential P19 cells is associated
with formation of cell lines that stably express multiple properties of
differentiated smooth muscle. It remains to be determined whether
retinoic acid has induced commitment to a smooth muscle cell lineage as
opposed to directly (or indirectly) activating genes characteristic of
differentiated smooth muscle cells. However, results suggest that this
cell system may be of use in attempting to identify genes involved in
controlling smooth muscle differentiation and/or lineage determination.
Key Words: smooth muscle differentiation • embryonal carcinoma cells • muscle-specific gene expression • homeobox genes • transcription factors
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