title: Transcriptional analysis of early lineage commitment in human embryonic stem cells.
abstract: BACKGROUND
  The mechanisms responsible for the maintenance of pluripotency in human embryonic stem cells, and those that drive their commitment into particular differentiation lineages, are poorly understood. In fact, even our knowledge of the phenotype of hESC is limited, because the immunological and molecular criteria presently used to define this phenotype describe the properties of a heterogeneous population of cells.
  
  
  RESULTS
  We used a novel approach combining immunological and transcriptional analysis (immunotranscriptional profiling) to compare gene expression in hESC populations at very early stages of differentiation. Immunotranscriptional profiling enabled us to identify novel markers of stem cells and their differentiated progeny, as well as novel potential regulators of hESC commitment and differentiation. The data show clearly that genes associated with the pluripotent state are downregulated in a coordinated fashion, and that they are co-expressed with lineage specific transcription factors in a continuum during the early stages of stem cell differentiation.
  
  
  CONCLUSIONS
  These findings, that show that maintenance of pluripotency and lineage commitment are dynamic, interactive processes in hESC cultures, have important practical implications for propagation and directed differentiation of these cells, and for the interpretation of mechanistic studies of hESC renewal and commitment. Since embryonic stem cells at defined stages of commitment can be isolated in large numbers by immunological means, they provide a powerful model for studying molecular genetics of stem cell commitment in the embryo.
authors.affiliation: Monash Institute of Medical Research, Monash University and the Australian Stem Cell Centre, Clayton, Victoria Australia. andrew.laslett@stemcellcentre.edu.au <andrew.laslett@stemcellcentre.edu.au>
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Laslett
authors.forename: Sean
authors.initials: S
authors.lastname: Grimmond
authors.forename: Brooke
authors.initials: B
authors.lastname: Gardiner
authors.forename: Lincon
authors.initials: L
authors.lastname: Stamp
authors.forename: Adelia
authors.initials: A
authors.lastname: Lin
authors.forename: Susan M
authors.initials: SM
authors.lastname: Hawes
authors.forename: Sam
authors.initials: S
authors.lastname: Wormald
authors.forename: David
authors.initials: D
authors.lastname: Nikolic-Paterson
authors.forename: David
authors.initials: D
authors.lastname: Haylock
authors.forename: Martin F
authors.initials: MF
authors.lastname: Pera
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology*; D019084:Fluorescent Antibody Technique, Indirect; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D039904:Pluripotent Stem Cells / Q000166:cytology*; D011994:Recombinant Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000235:genetics
chemical_list: D005819:Genetic Markers; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; C001643:podocalyxin