title: Transcriptome analysis of embryonic mammary cells reveals insights into mammary lineage establishment.
abstract: BACKGROUND
  The mammary primordium forms during embryogenesis as a result of inductive interactions between its constitutive tissues, the mesenchyme and epithelium, and represents the earliest evidence of commitment to the mammary lineage. Previous studies of embryonic mouse mammary epithelium indicated that, by mid-gestation, these cells are determined to a mammary cell fate and that a stem cell population has been delimited. Mammary mesenchyme can induce mammary development from simple epithelium even across species and classes, and can partially restore features of differentiated tissue to mouse mammary tumours in co-culture experiments. Despite these exciting properties, the molecular identity of embryonic mammary cells remains to be fully characterised.
  
  
  METHODS
  Here, we define the transcriptome of the mammary primordium and the two distinct cellular compartments that comprise it, the mammary primordial bud epithelium and mammary mesenchyme. Pathway and network analysis was performed and comparisons of embryonic mammary gene expression profiles to those of both postnatal mouse and human mammary epithelial cell sub-populations and stroma were made.
  
  
  RESULTS
  Several of the genes we have detected in our embryonic mammary cell signatures were previously shown to regulate mammary cell fate and development, but we also identified a large number of novel candidates. Additionally, we determined genes that were expressed by both embryonic and postnatal mammary cells, which represent candidate regulators of mammary cell fate, differentiation and progenitor cell function that could signal from mammary lineage inception during embryogenesis through postnatal development. Comparison of embryonic mammary cell signatures with those of human breast cells identified potential regulators of mammary progenitor cell functions conserved across species.
  
  
  CONCLUSIONS
  These results provide new insights into genetic regulatory mechanisms of mammary development, particularly identification of novel potential regulators of mammary fate and mesenchymal-epithelial cross-talk. Since cancers may represent diseases of mesenchymal-epithelial communications, we anticipate these results will provide foundations for further studies into the fundamental links between developmental, stem cell and breast cancer biology.
authors.affiliation: Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Olivia
authors.initials: O
authors.lastname: Wansbury
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay
authors.forename: Naoko
authors.initials: N
authors.lastname: Kogata
authors.forename: Costas
authors.initials: C
authors.lastname: Mitsopoulos
authors.forename: Howard
authors.initials: H
authors.lastname: Kendrick
authors.forename: Kathryn
authors.initials: K
authors.lastname: Davidson
authors.forename: Christiana
authors.initials: C
authors.lastname: Ruhrberg
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Smalley
authors.forename: Marketa
authors.initials: M
authors.lastname: Zvelebil
authors.forename: Beatrice A
authors.initials: BA
authors.lastname: Howard
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019070:Cell Lineage; D004847:Epithelial Cells / Q000502:physiology; D047628:Estrogen Receptor alpha; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D042361:Mammary Glands, Human / Q000166:cytology; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008815:Mice, Inbred Strains; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha