Gene expression in human embryonic stem cell lines: unique molecular signature.
Human embryonic stem (huES) cells have the ability to differentiate into a variety of cell lineages and potentially provide a source of differentiated cells for many therapeutic uses. However, little is known about the mechanism of differentiation of huES cells and factors regulating cell development. We have used high-quality microarrays containing 16 659 seventy-base pair oligonucleotides to examine gene expression in 6 of the 11 available huES cell lines. Expression was compared against pooled RNA from multiple tissues (universal RNA) and genes enriched in huES cells were identified. All 6 cell lines expressed multiple markers of the undifferentiated state and shared significant homology in gene expression (overall similarity coefficient > 0.85).A common subset of 92 genes was identified that included Nanog, GTCM-1, connexin 43 (GJA1), oct-4, and TDGF1 (cripto). Gene expression was confirmed by a variety of techniques including comparison with databases, reverse transcriptase-polymerase chain reaction, focused cDNA microarrays, and immunocytochemistry. Comparison with published "stemness" genes revealed a limited overlap, suggesting little similarity with other stem cell populations. Several novel ES cell-specific expressed sequence tags were identified and mapped to the human genome. These results represent the first detailed characterization of undifferentiated huES cells and provide a unique set of markers to profile and better understand the biology of huES cells.
Bhattacharya
Bhaskar
B
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Miura
Takumi
T
Brandenberger
Ralph
R
Mejido
Josef
J
Luo
Yongquan
Y
Yang
Amy X
AX
Joshi
Bharat H
BH
Ginis
Irene
I
Thies
R Scott
RS
Amit
Michal
M
Lyons
Ian
I
Condie
Brian G
BG
Itskovitz-Eldor
Joseph
J
Rao
Mahendra S
MS
Puri
Raj K
RK
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D019295:Computational Biology; D020224:Expressed Sequence Tags; D015870:Gene Expression; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D005819:Genetic Markers