Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation.
Human embryonic stem (hES) cells hold promise for generating an unlimited supply of cells for replacement therapies. To characterize hES cells at the molecular level, we obtained 148,453 expressed sequence tags (ESTs) from undifferentiated hES cells and three differentiated derivative subpopulations. Over 32,000 different transcripts expressed in hES cells were identified, of which more than 16,000 do not match closely any gene in the UniGene public database. Queries to this EST database revealed 532 significantly upregulated and 140 significantly downregulated genes in undifferentiated hES cells. These data highlight changes in the transcriptional network that occur when hES cells differentiate. Among the differentially regulated genes are several components of signaling pathways and transcriptional regulators that likely play key roles in hES cell growth and differentiation. The genomic data presented here may facilitate the derivation of clinically useful cell types from hES cells.
Brandenberger
Ralph
R
Geron Corporation, Menlo Park, California 94025, USA. rbrandenberger@geron.com
Wei
Henry
H
Zhang
Sally
S
Lei
Shirley
S
Murage
Jaji
J
Fisk
Gregory J
GJ
Li
Yan
Y
Xu
Chunhui
C
Fang
Rixun
R
Guegler
Karl
K
Rao
Mahendra S
MS
Mandalam
Ramumkar
R
Lebkowski
Jane
J
Stanton
Lawrence W
LW
D015703:Antigens, CD / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D050822:Cytokine Receptor gp130; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology; D020224:Expressed Sequence Tags; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D015723:Gene Library; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D055457:Nodal Protein; D011506:Proteins / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D051153:Wnt Proteins
D015703:Antigens, CD; D006133:Growth Substances; C494199:IL6ST protein, human; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008562:Membrane Glycoproteins; C526007:NODAL protein, human; D055457:Nodal Protein; D011506:Proteins; D011518:Proto-Oncogene Proteins; D017468:Receptors, Fibroblast Growth Factor; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D050822:Cytokine Receptor gp130; D014212:Tretinoin; D005346:Fibroblast Growth Factors; D012313:RNA; D004121:Dimethyl Sulfoxide