Gene expression profiling of embryo-derived stem cells reveals candidate genes associated with pluripotency and lineage specificity.
Large-scale gene expression profiling was performed on embryo-derived stem cell lines to identify molecular signatures of pluripotency and lineage specificity. Analysis of pluripotent embryonic stem (ES) cells, extraembryonic-restricted trophoblast stem (TS) cells, and terminally-differentiated mouse embryo fibroblast (MEF) cells identified expression profiles unique to each cell type, as well as genes common only to ES and TS cells. Whereas most of the MEF-specific genes had been characterized previously, the majority (67%) of the ES-specific genes were novel and did not include known differentiated cell markers. Comparison with microarray data from embryonic material demonstrated that ES-specific genes were underrepresented in all stages sampled, whereas TS-specific genes included known placental markers. Investigation of four novel TS-specific genes showed trophoblast-restricted expression in cell lines and in vivo, whereas one uncharacterized ES-specific gene, Esg-1, was found to be exclusively associated with pluripotency. We suggest that pluripotency requires a set of genes not expressed in other cell types, whereas lineage-restricted stem cells, like TS cells, express genes predictive of their differentiated lineage.
Tanaka
Tetsuya S
TS
Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, 21224-6820, USA.
Kunath
Tilo
T
Kimber
Wendy L
WL
Jaradat
Saied A
SA
Stagg
Carole A
CA
Usuda
Masayuki
M
Yokota
Takashi
T
Niwa
Hitoshi
H
Rossant
Janet
J
Ko
Minoru S H
MS
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology* / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D020043:Genes, Essential / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D005810:Multigene Family / Q000235:genetics; D050814:Octamer Transcription Factor-3; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D009928:Organ Specificity / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D011506:Proteins / Q000235:genetics; D039901:Totipotent Stem Cells / Q000737:chemistry / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics; D014327:Trophoblasts / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D029867:Xenopus Proteins
D051792:Basic Helix-Loop-Helix Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050814:Octamer Transcription Factor-3; D011506:Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; C494174:Pou5f1 protein, mouse; C108340:TLE1 protein, Xenopus