title: BMP induction of cardiogenesis in P19 cells requires prior cell-cell interaction(s).
abstract: Mouse P19 embryonal carcinoma cells undergo cardiogenesis in response to high density and DMSO. We have derived a clonal subline that undergoes cardiogenesis in response to high density, but without requiring exposure to DMSO. The new subline retains the capacity to differentiate into skeletal muscle and neuronal cells in response to DMSO and retinoic acid. However, upon aggregation, these Oct 4-positive cells, termed P19-SI because they "self-induce" cardiac muscle, exhibit increased mRNAs encoding the mesodermal factor Brachyury, cardiac transcription factors Nkx 2.5 and GATA 4, the transcriptional repressor Msx-1, and cytokines Wnt 3a, Noggin, and BMP 4. Exposure of aggregated P19-SI cells to BMP 4, a known inducer of cardiogenesis, accelerates cardiogenesis, as determined by rhythmic beating and myosin staining. However, cardiogenesis is severely inhibited when P19-SI cells are aggregated in the presence of BMP 4. These results demonstrate that cell-cell interaction is required before P19-SI cells can undergo a cardiogenic response to BMP 4. A concurrent increase in the expression of Msx-1 suggests one possible process underlying the inhibition of cardiogenesis. The phenotype of P19-SI cells offers an opportunity to explore new aspects of cardiac induction.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Angello
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kaestner
authors.forename: Robert E
authors.initials: RE
authors.lastname: Welikson
authors.forename: Jean N
authors.initials: JN
authors.lastname: Buskin
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Hauschka
mesh_terms: D000818:Animals; D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D048430:Cell Shape; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004707:Endoderm / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D051957:MSX1 Transcription Factor / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D015415:Biomarkers; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D051957:MSX1 Transcription Factor; C484084:Msx1 protein, mouse; D014212:Tretinoin; D004121:Dimethyl Sulfoxide