Genetic and Functional Differences between Multipotent Neural and Pluripotent Embryonic Stem Cells

Stem cells (SCs) are functionally defined by their abilities to self-renew and generate differentiated cells. Although much effort has been focused on defining the common characteristics among various types of SCs, the genetic and functional differences between multipotent and pluripotent SCs have g...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 100; no. Suppl 1; pp. 11866 - 11872
Main Authors D'Amour, Kevin A., Gage, Fred H.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 30.09.2003
National Acad Sciences
SeriesColloquium Paper
Subjects
Animals
Base Sequence
Blastocyst
Cell cycle
Colloquium Papers
Cultured cells
DNA, Complementary - genetics
DNA-Binding Proteins - genetics
Embryonic stem cells
Embryos
Fetus
Fluorescence
Gene Expression Profiling
Genes
Genetics
Green Fluorescent Proteins
HMGB Proteins
Luminescent Proteins - genetics
Mice
Mice, Transgenic
Multipotent stem cells
Multipotent Stem Cells - cytology
Multipotent Stem Cells - physiology
Neurons
Neurons - chemistry
Neurons - physiology
Nuclear Proteins - genetics
Pluripotent stem cells
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - physiology
Promoter Regions, Genetic
Recombinant Fusion Proteins - genetics
Reverse Transcriptase Polymerase Chain Reaction
SOXB1 Transcription Factors
Stem cells
Transcription Factors
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Summary:Stem cells (SCs) are functionally defined by their abilities to self-renew and generate differentiated cells. Although much effort has been focused on defining the common characteristics among various types of SCs, the genetic and functional differences between multipotent and pluripotent SCs have garnered less attention. We report a direct genetic and functional comparison of molecularly defined and clonally related populations of neural SCs (NSCs) and embryonic SCs (ESCs), using the Sox2 promoter for isolation of purified populations by fluorescence-activated cell sorting. A stringent expression profile comparison of promoter-defined NSCs and ESCs revealed a striking dissimilarity, and subsequent chimera analyses confirmed the fundamental differences in cellular potency between these populations. This direct comparison elucidates the molecular basis for the functional differences in pluripotent ESCs and multipotent NSCs.
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This paper results from the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Regenerative Medicine,” held October 18-22, 2002, at the Arnold and Mabel Beckman Center of the National Academies of Science and Engineering in Irvine, CA.
Abbreviations: SC, stem cell; EGFP, enhanced GFP; En, embryonic day n; ESC, embryonic SC; FACS, fluorescence-activated cell sorting; ICM, inner cell mass; NSC, neural stem cell; NSCc, cultured NSC; NSCf, freshly isolated NSC.
To whom correspondence should be addressed. E-mail: gage@salk.edu.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1834200100