Spontaneous differentiation of mouse embryonic stem cells in vitro: characterization by global gene expression profiles.
We characterized the temporal gene expression changes during four weeks of spontaneous differentiation of mouse ES cells in a monolayer culture in order to obtain better insight into the differentiation process. The overall gene expression pattern was changed dramatically during the first two weeks of spontaneous differentiation, but stabilized after the second week. Most of the genes regulated within the first two weeks of spontaneous differentiation were genes related to development including morphogenesis, cell differentiation, embryonic development, pattern specification, mesoderm development, post-embryonic development, and blastocyst development. While most of the ectoderm lineage related genes were down-regulated, genes related to the mesoderm or endoderm lineage were up-regulated through the first week and second week, respectively. This study revealed that the development of ectoderm lineage is a recessive process during the spontaneous differentiation of mouse ES cells in monolayer culture. Our time-course characterization might provide a useful time line for directed differentiation of mouse ES cells.
Heo
Jeonghoon
J
Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Lee
Ju-Seog
JS
Chu
In-Sun
IS
Takahama
Yasushi
Y
Thorgeirsson
Snorri S
SS
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D016000:Cluster Analysis; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012984:Software; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D014158:Transcription, Genetic; D015854:Up-Regulation
D018076:DNA, Complementary; D012313:RNA