Evidence map›Paper›PMID 23980595›Full record

ArticleStem cells and development2014

Identification of a developmental gene expression signature, including HOX genes, for the normal human colonic crypt stem cell niche: overexpression of the signature parallels stem cell overpopulation during colon tumorigenesis.

Seema Bhatlekar, Sankar Addya, Moreh Salunek, Christopher R Orr, Saul Surrey, Steven McKenzie, Jeremy Z Fields, Bruce M Boman

Abstract read
In one paragraph

Article in Stem cells and development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 48 citations in OpenAlex.

  1. Trial
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  3. Functional and Genetic Analyses Unveil the Implication ofJournal of developmental biology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Seema Bhatlekar1 Center for Translational Cancer Research, Helen F. Graham Cancer Center and Research Institute, University of Delaware , Newark, Delaware.
Sankar Addya
Moreh Salunek
Christopher R Orr
Saul Surrey
Steven McKenzie
Jeremy Z Fields
Bruce M Boman
Thomas Jefferson University · USSidney Kimmel Cancer Center · US

Funding

X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI DANIEL P SILVER · 1995 to 2026
$94.8M
Predictive Modeling & Optimal Control Framework for Model-Based Epidemic Response in DelawareP20GM103446 · NIGMS · UNIVERSITY OF DELAWARE · PI Anjana Narayan Bhat · 2012 to 2026
$67.2M
MARKERS FOR STEM CELL-LIKE COLONIC CRYPT BASE CELLSR21DK062146 · NIDDK · THOMAS JEFFERSON UNIVERSITY · PI BOMAN, BRUCE M · 2003 to 2004
$314k
NCI NIH HHS P30 CA056036NIDDK NIH HHS R21DK062146NIGMS NIH HHS P20 GM103446
6 · The paper itself

Abstract

Our goal was to identify a unique gene expression signature for human colonic stem cells (SCs). Accordingly, we determined the gene expression pattern for a known SC-enriched region--the crypt bottom. Colonic crypts and isolated crypt subsections (top, middle, and bottom) were purified from fresh, normal, human, surgical specimens. We then used an innovative strategy that used two-color microarrays (∼18,500 genes) to compare gene expression in the crypt bottom with expression in the other crypt subsections (middle or top). Array results were validated by PCR and immunostaining. About 25% of genes analyzed were expressed in crypts: 88 preferentially in the bottom, 68 in the middle, and 131 in the top. Among genes upregulated in the bottom, ∼30% were classified as growth and/or developmental genes including several in the PI3 kinase pathway, a six-transmembrane protein STAMP1, and two homeobox (HOXA4, HOXD10) genes. qPCR and immunostaining validated that HOXA4 and HOXD10 are selectively expressed in the normal crypt bottom and are overexpressed in colon carcinomas (CRCs). Immunostaining showed that HOXA4 and HOXD10 are co-expressed with the SC markers CD166 and ALDH1 in cells at the normal crypt bottom, and the number of these co-expressing cells is increased in CRCs. Thus, our findings show that these two HOX genes are selectively expressed in colonic SCs and that HOX overexpression in CRCs parallels the SC overpopulation that occurs during CRC development. Our study suggests that developmental genes play key roles in the maintenance of normal SCs and crypt renewal, and contribute to the SC overpopulation that drives colon tumorigenesis.

Indexed as

Cell Transformation, NeoplasticColonColonic NeoplasmsGene Expression Regulation, DevelopmentalHomeodomain ProteinsHumansIntestinal MucosaMembrane ProteinsNeoplasm ProteinsOligonucleotide Array Sequence AnalysisOxidoreductasesRNA, MessengerStem CellsTranscription FactorsHomeodomain ProteinsHOXA4 protein, humanHOXD10 protein, humanMembrane ProteinsNeoplasm ProteinsOxidoreductasesRNA, MessengerSTEAP2 protein, humanTranscription Factors

Identifiers

PMID23980595
PMCPMC3887463
OpenAlexW2096124964

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.