title: Discovery of progenitor cell signatures by time-series synexpression analysis during Drosophila embryonic cell immortalization.
abstract: The use of time series profiling to identify groups of functionally related genes (synexpression groups) is a powerful approach for the discovery of gene function. Here we apply this strategy during Ras(V12) immortalization of Drosophila embryonic cells, a phenomenon not well characterized. Using high-resolution transcriptional time-series datasets, we generated a gene network based on temporal expression profile similarities. This analysis revealed that common immortalized cells are related to adult muscle precursors (AMPs), a stem cell-like population contributing to adult muscles and sharing properties with vertebrate satellite cells. Remarkably, the immortalized cells retained the capacity for myogenic differentiation when treated with the steroid hormone ecdysone. Further, we validated in vivo the transcription factor CG9650, the ortholog of mammalian Bcl11a/b, as a regulator of AMP proliferation predicted by our analysis. Our study demonstrates the power of time series synexpression analysis to characterize Drosophila embryonic progenitor lines and identify stem/progenitor cell regulators.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, mdequeant@genetics.med.harvard.edu perrimon@receptor.med.harvard.edu.
authors.forename: Mary-Lee
authors.initials: ML
authors.lastname: Dequéant
authors.affiliation: Cold Spring Harbor Laboratories, Cold Spring Harbor, NY 11724;
authors.forename: Delphine
authors.initials: D
authors.lastname: Fagegaltier
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Spirohn
authors.affiliation: Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210;
authors.forename: Amanda
authors.initials: A
authors.lastname: Simcox
authors.affiliation: Howard Hughes Medical Institute, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY 11724;
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115 mdequeant@genetics.med.harvard.edu perrimon@receptor.med.harvard.edu.
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D004330:Drosophila / Q000196:embryology*; D004625:Embryo, Nonmammalian / Q000166:cytology; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D014158:Transcription, Genetic
chemical_list: D016160:Retinoblastoma Protein
keywords: Drosophila; RNA-Seq; immortalization; time series