Evidence map›Paper›PMID 17577930›Full record

ArticleExperimental hematology2007

Near-maximal expansions of hematopoietic stem cells in culture using NUP98-HOX fusions.

Hideaki Ohta, Sanja Sekulovic, Silvia Bakovic, Connie J Eaves, Nicolas Pineault, Maura Gasparetto, Clayton Smith, Guy Sauvageau, R Keith Humphries

Open access · greenAbstract read
In one paragraph

Article in Experimental hematology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

31 citing papers in PubMed, 58 citations in OpenAlex.

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  20. A role for GPx3 in activity of normal and leukemia stem cells.The Journal of experimental medicine · 2012
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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

9 authors at 3 institutions in 1 country.

Hideaki OhtaTerry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Sanja Sekulovic
Silvia Bakovic
Connie J Eaves
Nicolas Pineault
Maura Gasparetto
Clayton Smith
Guy Sauvageau
R Keith Humphries
BC Cancer Agency · CAUniversity of British Columbia · CAInstitute for Research in Immunology and Cancer · CA

Funding

HOXB4 Is An Activator of HSC Self-RenewalR01HL065430 · NHLBI · UNIVERSITY OF MONTREAL · PI SAUVAGEAU, GUY · 2001 to 2009
$2.6M
NHLBI NIH HHS R01 HL065430NHLBI NIH HHS R01 HL065430-06
6 · The paper itself

Abstract

objectiveStrategies to expand hematopoietic stem cells (HSCs) ex vivo are of key interest. The objective of this study was to resolve if ability of HOXB4, previously documented to induce a significant expansion of HSCs in culture, may extend to other HOX genes and also to further analyze the HOX sequence requirements to achieve this effect.

methodsTo investigate the ability of Nucleoporin98-Homeobox fusion genes to stimulate HSC self-renewal, we evaluated their presence in 10- to 20-day cultures of transduced mouse bone marrow cells. Stem cell recovery was measured by limiting-dilution assay for long-term competitive repopulating cells (CRU Assay).

resultsThese experiments revealed remarkable expansions of Nucleoporin98-Homeobox-transduced HSCs (1000-fold to 10,000-fold over input) in contrast to the expected decline of HSCs in control cultures. Nevertheless, the Nucleoporin98-Homeobox-expanded HSCs displayed no proliferative senescence and retained normal lympho-myeloid differentiation activity and a controlled pool size in vivo. Analysis of proviral integration patterns showed the cells regenerated in vivo were highly polyclonal, indicating they had derived from a large proportion of the initially targeted HSCs. Importantly, these effects were preserved when all HOX sequences flanking the homeodomain were removed, thus defining the homeodomain as a key and independent element in the fusion.

conclusionThese findings create new possibilities for investigating HSCs biochemically and genetically and for achieving clinically significant expansion of human HSCs.

Indexed as

AnimalsCell Culture TechniquesHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHomeobox A10 ProteinsHomeodomain ProteinsMiceMice, Inbred C57BLNuclear Pore Complex ProteinsRecombinant Fusion ProteinsTranscription FactorsHomeobox A10 ProteinsHomeodomain ProteinsHoxa10 protein, mouseHoxb4 protein, mousenuclear pore complex protein 98Nuclear Pore Complex ProteinsRecombinant Fusion ProteinsTranscription Factors

Identifiers

PMID17577930
PMCPMC2774852
OpenAlexW2149547604

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.