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Cited by 86Cancer Cells and MetastasisPluripotent Stem Cells ResearchDevelopmental Biology and Gene Regulation

A gene expression profile of stem cell pluripotentiality and differentiation is conserved across diverse solid and hematopoietic cancers

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Palmer, Nathan P, Schmid, Patrick R, Berger, Bonnie, Kohane, Isaac S·2012·Genome Biology
DOI 10.1186/gb-2012-13-8-r71PMC PMC3491371
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Abstract

Background: Understanding the fundamental mechanisms of tumorigenesis remains one of the most pressing problems in modern biology. To this end, stem-like cells with tumor-initiating potential have become a central focus in cancer research. While the cancer stem cell hypothesis presents a compelling model of self-renewal and partial differentiation, the relationship between tumor cells and normal stem cells remains unclear. Results: We identify, in an unbiased fashion, mRNA transcription patterns associated with pluripotent stem cells. Using this profile, we derive a quantitative measure of stem cell-like gene expression activity. We show how this 189 gene signature stratifies a variety of stem cell, malignant and normal tissue samples by their relative plasticity and state of differentiation within Concordia, a diverse gene expression database consisting of 3,209 Affymetrix HGU133+ 2.0 microarray assays. Further, the orthologous murine signature correctly orders a time course of differentiating embryonic mouse stem cells. Finally, we demonstrate how this stem-like signature serves as a proxy for tumor grade in a variety of solid tumors, including brain, breast, lung and colon. Conclusions: This core stemness gene expression signature represents a quantitative measure of stem cell-associated transcriptional activity. Broadly, the intensity of this signature correlates to the relative level of plasticity and differentiation across all of the human tissues analyzed. The fact that the intensity of this signature is also capable of differentiating histological grade for a variety of human malignancies suggests potential therapeutic and diagnostic implications.

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  • Epithelial cell dedifferentiation is a critical cell state transition during tumorigenesis and confers tumor cells high proliferation capacity and progenitor-like fate through multidimensional reprogramming.

    “Epithelial cell dedifferentiation is recognized as a critical cell state transition during tumorigenesis and confer tumor cells on high proliferation capacity and progenitor-like fate through multidimensional reprogramming1–3.”

    From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [2]

    The Background describes cancers as showing stem cell-like programming and shared proliferative potential, and the Conclusions describe stem cell-specific expression in tumor samples. Neither section establishes epithelial-cell dedifferentiation as a critical transition during tumorigenesis or shows that multidimensional reprogramming confers proliferation and progenitor-like fate. Page numbers are unavailable in our copy. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Palmer, N. P., Schmid, P. R., Berger, B., & Kohane, I. S.
Affiliations
  • MIT Computer Science and Artificial Intelligence Laboratory (US)
  • Harvard University (US)
Corresponding author
  • Berger, Bonnie
  • Kohane, Isaac S
ORCID
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2012-08-21
Volume
13
Issue
8
Pages
R71-R71
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
DOI
10.1186/gb-2012-13-8-r71
PMC
PMC3491371
OpenAlex
W2109095750
Cited by
86
References
1
Citations by year
2026: 3 · 2025: 4 · 2024: 7 · 2023: 9 · 2022: 8 · 2021: 9 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 6 · 2016: 5 · 2015: 6 · 2014: 7 · 2013: 7 · 2012: 1
FWCI
3.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
Funders
  • National Institutes of Health (5r01lm010125-02, LM008748)
  • National Institute of General Medical Sciences (R01GM081871)
  • U.S. National Library of Medicine (U54LM008748, R01LM010125-02)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
cancer stem cells, pluripotency, cell differentiation, tumor grade, solid tumors, hematopoietic tumors, embryonic stem cell differentiation, tissue plasticity, gene expression profiling
MeSH terms
Animals, Cell Differentiation, Cell Line, Cell Transformation, Neoplastic, Humans, Transcription, Genetic, Databases, Genetic, Pluripotent Stem Cells, Microarray Analysis, Cell Proliferation, Mice, Embryonic Stem Cells, Transcriptome

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