Home LiteratureArticle Details
PMID: 17560561 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Intramural

Global gene expression profiling reveals similarities and differences among mouse pluripotent stem cells of different origins and strains.

Developmental biology ·Vol. 307 ·No. 2 ·2007-07-15 ·Pages 446-59

Sharova LV, Sharov AA, Piao Y, Shaik N, Sullivan T, Stewart CL, Hogan BL, Ko MS

Abstract

Pluripotent stem cell lines with similar phenotypes can be derived from both blastocysts (embryonic stem cells, ESC) and primordial germ cells (embryonic germ cells, EGC). Here, we present a compendium DNA microarray analysis of multiple mouse ESCs and EGCs from different genetic backgrounds (strains 129 and C57BL/6) cultured under standard conditions and in differentiation-promoting conditions by the withdrawal of Leukemia Inhibitory Factor (LIF) or treatment with retinoic acid (RA). All pluripotent cell lines showed similar gene expression patterns, which separated them clearly from other tissue stem cells with lower developmental potency. Differences between pluripotent lines derived from different sources (ESC vs. EGC) were smaller than differences between lines derived from different mouse strains (129 vs. C57BL/6). Even in the differentiation-promoting conditions, these pluripotent cells showed the same general trends of gene expression changes regardless of their origin and genetic background. These data indicate that ESCs and EGCs are indistinguishable based on global gene expression patterns alone. On the other hand, a detailed comparison between a group of ESC lines and a group of EGC lines identified 20 signature genes whose average expression levels were consistently higher in ESC lines, and 84 signature genes whose average expression levels were consistently higher in EGC lines, irrespective of mouse strains. Similar analysis identified 250 signature genes whose average expression levels were consistently higher in a group of 129 cell lines, and 337 signature genes whose average expression levels were consistently higher in a group of C57BL/6 cell lines. Although none of the genes was exclusively expressed in either ESCs versus EGCs or 129 versus C57BL/6, in combination these signature genes provide a reliable separation and identification of each cell type. Differentiation-promoting conditions also revealed some minor differences between the cell lines. For example, in the presence of RA, EGCs showed a lower expression of muscle- and cardiac-related genes and a higher expression of gonad-related genes than ESCs. Taken together, the results provide a rich source of information about the similarities and differences between ESCs and EGCs as well as 129 lines and C57BL/6 lines. Such information will be crucial to our understanding of pluripotent stem cells. The results also underscore the importance of studying multiple cell lines from different strains when making comparisons based on gene expression analysis.

MeSH Terms
Animals Cell Cycle Cell Differentiation/drug effects Cell Line Embryonic Stem Cells/cytology,drug effects,metabolism Female Gene Expression Profiling Leukemia Inhibitory Factor/pharmacology Male Mice Mice, Inbred C57BL Oligonucleotide Array Sequence Analysis Phenotype Pluripotent Stem Cells/cytology,drug effects,metabolism Species Specificity Tretinoin/pharmacology
Chemicals
Leukemia Inhibitory Factor Lif protein, mouse Tretinoin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Sharova Lioudmila V
Laboratory of Genetics, National Institute on Aging, NIH, 333 Cassell Drive, Suite 3000, Baltimore, MD 21224, USA.
Sharov Alexei A
Piao Yulan
Shaik Nabeebi
Sullivan Terry
Stewart Colin L
Hogan Brigid L M
Ko Minoru S H
References (70)
70 references, click to expand
  1. Obox, a family of homeobox genes preferentially expressed in germ cells.
    Genomics. 2002 May;79(5):711-7 PMID: 11991721
  2. A germ cell origin of embryonic stem cells?
    Development. 2005 Jan;132(2):227-33 PMID: 15623802
  3. Pluripotential stem cells derived from migrating primordial germ cells.
    Differentiation. 2001 Oct;68(4-5):220-6 PMID: 11776474
  4. Significant variations in differentiation properties between independent mouse ES cell lines cultured under defined conditions.
    Exp Cell Res. 2004 Feb 15;293(2):229-38 PMID: 14729460
  5. Core transcriptional regulatory circuitry in human embryonic stem cells.
    Cell. 2005 Sep 23;122(6):947-56 PMID: 16153702
  6. Mouse embryonic germ (EG) cell lines: transmission through the germline and differences in the methylation imprint of insulin-like growth factor 2 receptor (Igf2r) gene compared with embryonic stem (ES) cell lines.
    Development. 1994 Nov;120(11):3197-204 PMID: 7720562
  7. "Stemness": transcriptional profiling of embryonic and adult stem cells.
    Science. 2002 Oct 18;298(5593):597-600 PMID: 12228720
  8. High-throughput screen for genes predominantly expressed in the ICM of mouse blastocysts by whole mount in situ hybridization.
    Gene Expr Patterns. 2006 Jan;6(2):213-24 PMID: 16325481
  9. Primordial germ cell-derived mouse embryonic germ (EG) cells in vitro resemble undifferentiated stem cells with respect to differentiation capacity and cell cycle distribution.
    Cell Biol Int. 1996 Aug;20(8):579-87 PMID: 8938992
  10. The influence of genetic background on the induction of oxidative stress and impaired insulin secretion in mouse islets.
    Diabetologia. 2006 Jun;49(6):1254-63 PMID: 16570159
  11. Id genes are direct targets of bone morphogenetic protein induction in embryonic stem cells.
    J Biol Chem. 1999 Jul 9;274(28):19838-45 PMID: 10391928
  12. Novel role for the orphan nuclear receptor Dax1 in embryogenesis, different from steroidogenesis.
    Mol Genet Metab. 2006 Jul;88(3):261-71 PMID: 16466956
  13. A stem cell molecular signature.
    Science. 2002 Oct 18;298(5593):601-4 PMID: 12228721
  14. Embryo-derived stem cells: of mice and men.
    Annu Rev Cell Dev Biol. 2001;17:435-62 PMID: 11687496
  15. Lineage choice and differentiation in mouse embryos and embryonic stem cells.
    Dev Biol. 2003 Dec 1;264(1):1-14 PMID: 14623228
  16. ES cells derived from cloned and fertilized blastocysts are transcriptionally and functionally indistinguishable.
    Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):933-8 PMID: 16418286
  17. Embryonic stem cell lines derived from human blastocysts.
    Science. 1998 Nov 6;282(5391):1145-7 PMID: 9804556
  18. Establishment in culture of pluripotential cells from mouse embryos.
    Nature. 1981 Jul 9;292(5819):154-6 PMID: 7242681
  19. Defining a developmental path to neural fate by global expression profiling of mouse embryonic stem cells and adult neural stem/progenitor cells.
    Stem Cells. 2006 Apr;24(4):889-95 PMID: 16357342
  20. Requirement for Foxd3 in maintaining pluripotent cells of the early mouse embryo.
    Genes Dev. 2002 Oct 15;16(20):2650-61 PMID: 12381664
  21. Stem cells from primordial germ cells can reenter the germ line.
    Dev Biol. 1994 Feb;161(2):626-8 PMID: 8314005
  22. Genetic susceptibility to irritant-induced acute lung injury in mice.
    Am J Physiol Lung Cell Mol Physiol. 2000 Sep;279(3):L575-82 PMID: 10956633
  23. Comparisons between transcriptional regulation and RNA expression in human embryonic stem cell lines.
    Stem Cells Dev. 2006 Jun;15(3):315-23 PMID: 16846370
  24. A polyoma-based episomal vector efficiently expresses exogenous genes in mouse embryonic stem cells.
    Nucleic Acids Res. 1996 Oct 1;24(19):3707-13 PMID: 8871548
  25. Long-term proliferation of mouse primordial germ cells in culture.
    Nature. 1992 Oct 8;359(6395):550-1 PMID: 1383830
  26. Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture.
    Cell. 1992 Sep 4;70(5):841-7 PMID: 1381289
  27. Pluripotency of spermatogonial stem cells from adult mouse testis.
    Nature. 2006 Apr 27;440(7088):1199-203 PMID: 16565704
  28. SAGE identification of gene transcripts with profiles unique to pluripotent mouse R1 embryonic stem cells.
    Genomics. 2002 Feb;79(2):169-76 PMID: 11829487
  29. Pluripotency of mesenchymal stem cells derived from adult marrow.
    Nature. 2002 Jul 4;418(6893):41-9 PMID: 12077603
  30. A web-based tool for principal component and significance analysis of microarray data.
    Bioinformatics. 2005 May 15;21(10):2548-9 PMID: 15734774
  31. Gene expression profiling of embryo-derived stem cells reveals candidate genes associated with pluripotency and lineage specificity.
    Genome Res. 2002 Dec;12(12):1921-8 PMID: 12466296
  32. Derivation of pluripotent stem cells from cultured human primordial germ cells.
    Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13726-31 PMID: 9811868
  33. Regulation of growth and metabolism by imprinted genes.
    Cytogenet Genome Res. 2006;113(1-4):279-91 PMID: 16575191
  34. Maternal germ-line transmission of mutant mtDNAs from embryonic stem cell-derived chimeric mice.
    Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14461-6 PMID: 11106380
  35. Migration of human and mouse primordial germ cells and colonization of the developing ovary: an ultrastructural and cytochemical study.
    Microsc Res Tech. 2006 Jun;69(6):386-95 PMID: 16718662
  36. The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium.
    J Embryol Exp Morphol. 1985 Jun;87:27-45 PMID: 3897439
  37. Expression profile viewer (ExProView): a software tool for transcriptome analysis.
    Genomics. 2000 Feb 1;63(3):341-53 PMID: 10704282
  38. Transcript copy number estimation using a mouse whole-genome oligonucleotide microarray.
    Genome Biol. 2005;6(7):R61 PMID: 15998450
  39. The stem cells of early embryos.
    Differentiation. 2001 Oct;68(4-5):159-66 PMID: 11776468
  40. NCBI GEO: mining tens of millions of expression profiles--database and tools update.
    Nucleic Acids Res. 2007 Jan;35(Database issue):D760-5 PMID: 17099226
  41. Evidence for genetic modifiers of ovarian follicular endowment and development from studies of five inbred mouse strains.
    Endocrinology. 2003 Jan;144(1):9-12 PMID: 12488324
  42. Nuclear reprogramming and pluripotency.
    Nature. 2006 Jun 29;441(7097):1061-7 PMID: 16810240
  43. Generation of pluripotent stem cells from neonatal mouse testis.
    Cell. 2004 Dec 29;119(7):1001-12 PMID: 15620358
  44. Search for testicular cancer gene hits dead-end.
    Cell Cycle. 2005 Sep;4(9):1136-8 PMID: 16082220
  45. cDNA cloning and expression of the human NOBOX gene in oocytes and ovarian follicles.
    Mol Hum Reprod. 2006 May;12(5):283-9 PMID: 16597639
  46. Differentiation of embryonic stem cells after transplantation into peritoneal cavity of irradiated mice and expression of specific germ cell genes in pluripotent cells.
    Transplant Proc. 2005 Jan-Feb;37(1):295-8 PMID: 15808624
  47. To knockout in 129 or in C57BL/6: that is the question.
    Trends Genet. 2004 Feb;20(2):59-62 PMID: 14746984
  48. Genome-wide assembly and analysis of alternative transcripts in mouse.
    Genome Res. 2005 May;15(5):748-54 PMID: 15867436
  49. Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4.
    Blood. 2005 Jan 15;105(2):635-7 PMID: 15358627
  50. The Ter mutation in the dead end gene causes germ cell loss and testicular germ cell tumours.
    Nature. 2005 May 19;435(7040):360-4 PMID: 15902260
  51. Epigenotype switching of imprintable loci in embryonic germ cells.
    Dev Genes Evol. 1998 Feb;207(8):551-61 PMID: 9510550
  52. Germ cells and pluripotent stem cells in the mouse.
    Reprod Fertil Dev. 2001;13(7-8):661-4 PMID: 11999318
  53. Withdrawal of differentiation inhibitory activity/leukemia inhibitory factor up-regulates D-type cyclins and cyclin-dependent kinase inhibitors in mouse embryonic stem cells.
    Oncogene. 1996 Jan 18;12(2):309-22 PMID: 8570208
  54. Immortal germ cells?
    Curr Biol. 1993 Jan;3(1):47-9 PMID: 15335881
  55. In situ-synthesized novel microarray optimized for mouse stem cell and early developmental expression profiling.
    Genome Res. 2003 May;13(5):1011-21 PMID: 12727912
  56. The modulatory role of transforming growth factor beta1 and androstenedione on follicle-stimulating hormone-induced gelatinase secretion and steroidogenesis in rat granulosa cells.
    Biol Reprod. 2004 May;70(5):1292-8 PMID: 14711789
  57. Embryonic stem cells and gene targeting.
    Exp Physiol. 2000 Nov;85(6):603-13 PMID: 11187956
  58. Transcriptome analysis of mouse stem cells and early embryos.
    PLoS Biol. 2003 Dec;1(3):E74 PMID: 14691545
  59. Cannabinoid-serotonin interactions in alcohol-preferring vs. alcohol-avoiding mice.
    J Neurochem. 2006 Oct;99(1):308-20 PMID: 16987253
  60. The putative human stem cell marker, Rex-1 (Zfp42): structural classification and expression in normal human epithelial and carcinoma cell cultures.
    Mol Carcinog. 2006 Dec;45(12):887-900 PMID: 16865673
  61. Turning germ cells into stem cells.
    Curr Opin Genet Dev. 2003 Oct;13(5):463-71 PMID: 14550410
  62. Gene expression profiling of mouse embryonic stem cell subpopulations.
    Biol Reprod. 2006 Oct;75(4):555-61 PMID: 16687650
  63. Comparison of thiol redox state of mitochondria and homogenates of various tissues between two strains of mice with different longevities.
    Exp Gerontol. 2004 Oct;39(10):1513-9 PMID: 15501021
  64. Developmental fate of embryonic germ cells (EGCs), in vivo and in vitro.
    Differentiation. 2003 Mar;71(2):135-41 PMID: 12641567
  65. Genome-wide prediction of imprinted murine genes.
    Genome Res. 2005 Jun;15(6):875-84 PMID: 15930497
  66. An efficient system to establish multiple embryonic stem cell lines carrying an inducible expression unit.
    Nucleic Acids Res. 2005;33(4):e43 PMID: 15741176
  67. Relationships between the expressions of CDX1 and CDX2 mRNA and clinicopathologic features in colorectal cancers.
    Korean J Intern Med. 2005 Dec;20(4):317-24 PMID: 16491830
  68. Transcriptome profiling of human and murine ESCs identifies divergent paths required to maintain the stem cell state.
    Stem Cells. 2005 Feb;23(2):166-85 PMID: 15671141
  69. Routine expression profiling of microarray gene signatures in acute leukaemia by real-time PCR of human bone marrow.
    Br J Haematol. 2005 Jul;130(2):233-48 PMID: 16029452
  70. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells.
    Proc Natl Acad Sci U S A. 1981 Dec;78(12):7634-8 PMID: 6950406
Article Info
Journal
Developmental biology
Abbr.
Dev Biol
ISSN
0012-1606
DOI
10.1016/j.ydbio.2007.05.004
Published
2007-07-15
Epub
2007-00-10
Pages
446-59
Language
English
Region
United States
NLM ID
0372762
PMCID
PMC2000702
Subset
IM
Grants
Intramural NIH HHS · Z01 AG000662-07 · United States
External Links
PubMed source DOI: 10.1016/j.ydbio.2007.05.004 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2