title: Molecular aspects of adipoepithelial transdifferentiation in mouse mammary gland.
abstract: The circular, reversible conversion of the mammary gland during pregnancy and involution is a paradigm of physiological tissue plasticity. The two most prominent cell types in mammary gland, adipocytes and epithelial cells, interact in an orchestrated way to coordinate this process. Previously, we showed that this conversion is at least partly achieved by reciprocal transdifferentiation between mammary adipocytes and lobulo-alveolar epithelial cells. Here, we aim to shed more light on the regulators of mammary transdifferentiation. Using immunohistochemistry with cell type-specific lipid droplet-coating markers (Perilipin1 and 2), we show that cells with an intermediate adipoepithelial phenotype exist during and after pregnancy. Nuclei of cells with similar transitional structural characteristics are highly positive for Elf5, a master regulator of alveologenesis. In cultured adipocytes, we could show that transient and stable ectopic expression of Elf5 induces expression of the milk component whey acidic protein, although the general adipocyte phenotype is not affected suggesting that additional pioneering factors are necessary. Furthermore, the lack of transdifferentiation of adipocytes during pregnancy after clearing of the epithelial compartment indicates that transdifferentiation signals must emanate from the epithelial part. To explore candidate genes potentially involved in the transdifferentiation process, we devised a high-throughput gene expression study to compare cleared mammary fat pads with developing, contralateral controls at several time points during pregnancy. Incorporation of bioinformatic predictions of secretory proteins provides new insights into possible paracrine signaling pathways and downstream transdifferentiation factors. We discuss a potential role for osteopontin (secreted phosphoprotein 1 [Spp1]) signaling through integrins to induce adipoepithelial transdifferentiation.
authors.affiliation: Institute for Genomics and Bioinformatics, Graz University of Technology, Petersgasse, Graz, Austria; Institute of Biochemistry, Graz University of Technology, Petersgasse, Graz, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Prokesch
authors.forename: A
authors.initials: A
authors.lastname: Smorlesi
authors.forename: J
authors.initials: J
authors.lastname: Perugini
authors.forename: M
authors.initials: M
authors.lastname: Manieri
authors.forename: P
authors.initials: P
authors.lastname: Ciarmela
authors.forename: E
authors.initials: E
authors.lastname: Mondini
authors.forename: Z
authors.initials: Z
authors.lastname: Trajanoski
authors.forename: K
authors.initials: K
authors.lastname: Kristiansen
authors.forename: A
authors.initials: A
authors.lastname: Giordano
authors.forename: J G
authors.initials: JG
authors.lastname: Bogner-Strauss
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinti
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002451:Cell Compartmentation; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology*; D051379:Mice; D008892:Milk / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D019899:Paracrine Communication; D010641:Phenotype; D011247:Pregnancy; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C500759:Elf5 protein, mouse; D014157:Transcription Factors
keywords: Adipocytes; Cell transdifferentiation; Elf5 protein; Mouse mammary gland; Spp1 protein