title: The genomic and proteomic blueprint of mouse megakaryocytes derived from embryonic stem cells.
abstract: BACKGROUND
  Platelets are specialized cells, produced by megakaryocytes (MKs) in the bone marrow, which represent the first defense against hemorrhage. There are many diseases where platelet production or function is impaired, with severe consequences for patients. Therefore, new insights into the process of MK differentiation and platelet formation would have a major impact on both basic and clinical research.
  
  
  OBJECTIVE
  Embryonic stem (ES) cells represent a good in vitro model to study the differentiation of MKs, with the possibility of being genetically engineered and constituting an unlimited source of MKs. However, lack of knowledge about the molecular identity of ES-derived MKs (ES-MKs) may prevent any further development and application of this model.
  
  
  METHODS
  This paper presents the first comprehensive transcriptional and proteome profile analyses of mouse ES-MKs in comparison with MKs derived from mouse fetal liver progenitors (FL-MKs).
  
  
  RESULTS
  In ES-MKs we found a down-regulation of cytoskeleton proteins, specific transcription factors and membrane receptors at both transcriptional and protein levels. At the phenotypic level, this molecular blueprint was displayed by ES-MKs' lower polyploidy, lower nuclear/cytoplasm ratio and reduced capacity to form proplatelets and releasing platelets.
  
  
  CONCLUSIONS
  Overall our data demonstrate that ES-MKs represent a useful model to clarify many aspects of both MK physiology and pathological conditions where impaired MK functions are related to defective MK development, as in inherited thrombocytopenias and primary myelofibrosis.
authors.affiliation: Laboratorio di Biologia dello Sviluppo, Dipartimento di Biologia e Biotecnologie Lazzaro Spallanzani, University of Pavia, Pavia, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Merico
authors.forename: M
authors.initials: M
authors.lastname: Zuccotti
authors.forename: D
authors.initials: D
authors.lastname: Carpi
authors.forename: D
authors.initials: D
authors.lastname: Baev
authors.forename: F
authors.initials: F
authors.lastname: Mulas
authors.forename: L
authors.initials: L
authors.lastname: Sacchi
authors.forename: R
authors.initials: R
authors.lastname: Bellazzi
authors.forename: R
authors.initials: R
authors.lastname: Pastorelli
authors.forename: C A
authors.initials: CA
authors.lastname: Redi
authors.forename: R
authors.initials: R
authors.lastname: Moratti
authors.forename: S
authors.initials: S
authors.lastname: Garagna
authors.forename: A
authors.initials: A
authors.lastname: Balduini
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D048430:Cell Shape / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers; D023281:Genomics / Q000379:methods; D005838:Genotype; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008533:Megakaryocytes / Q000378:metabolism*; D051379:Mice; D010641:Phenotype; D011003:Ploidies; D040901:Proteomics / Q000379:methods; D034061:Thrombopoiesis / Q000235:genetics
chemical_list: D005819:Genetic Markers