Gene discovery by microarray: identification of novel genes induced during growth factor-mediated muscle cell survival and differentiation.
Peptide growth factors regulate cell fate by activating distinct signal transduction pathways that ultimately influence gene expression. Insulin-like growth factors (IGFs) play central roles in controlling somatic growth and participate in skeletal muscle development and regeneration. In cultured muscle cells, IGF action is critical both for maintaining viability during the transition from proliferating to differentiating myoblasts and for facilitating differentiation. By contrast, platelet-derived growth factor (PDGF) can sustain cell survival but inhibits differentiation. Here we examine the genetic programs that accompany IGF and PDGF action in myoblasts. Through analysis of high-density oligonucleotide arrays containing approximately 36,000 mouse probe sets, we identify 90 transcripts differentially induced by IGF-I, including 28 muscle-specific genes and 33 previously unannotated mRNAs, and 55 transcripts specifically stimulated by PDGF, including 14 unknowns. Detailed study of one IGF-induced mRNA shows that it encodes a protein related to a recently characterized repulsive guidance molecule postulated to regulate neuronal targeting during development. Our results demonstrate the power of transcriptional profiling for gene discovery and provide opportunities for investigating new proteins potentially involved in different aspects of growth factor action in muscle.
Molecular Medicine Division, HRC 3, Department of Medicine, Oregon Health & Sciences University, Portland, OR 97239-3098, USA.
David
D
Kuninger
Ryan
R
Kuzmickas
Bonnie
B
Peng
John E
JE
Pintar
Peter
P
Rotwein
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000254:growth & development; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology / Q000502:physiology*
D010982:Platelet-Derived Growth Factor; D007334:Insulin-Like Growth Factor I