Evidence map›Paper›PMID 10421636›Full record

ArticleGenes & development1999

A GATA-2/estrogen receptor chimera functions as a ligand-dependent negative regulator of self-renewal.

C Heyworth, K Gale, M Dexter, G May, T Enver

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
–field-weighted citation impact
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

28 citing papers in PubMed, 87 citations in OpenAlex.

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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

5 authors at 4 institutions in 1 country.

C HeyworthCancer Research Campaign (CRC) Section of Hematopoietic Cell and Gene Therapeutics, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester M20 4BX, UK.
K Gale
M Dexter
G May
T Enver
Cancer Research UK · GBCancer Research UK Manchester Institute · GBInstitute of Cancer Research · GBNational Health Service · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

The transcription factor GATA-2 is expressed in hematopoietic stem and progenitor cells and is functionally implicated in their survival and proliferation. We have used estrogen and tamoxifen-inducible forms of GATA-2 to modulate the levels of GATA-2 in the IL-3-dependent multipotential hematopoietic progenitor cell model FDCP mix. Ligand-dependent induction of exogenous GATA-2 activity did not rescue cells deprived of IL-3 from apoptosis. However, induction of GATA-2 activity in cells cultured in IL-3 blocked factor-dependent self-renewal but not factor-dependent survival: Cells undergo cell cycle arrest and cease proliferating but do not apoptose. This was accompanied by differentiation down the monocytic and granulocytic pathways. Differentiation occurred in the presence of IL-3 and did not require addition of exogenous differentiation growth factors such as G-CSF or GM-CSF normally required to induce granulomonocytic differentiation of FDCP-mix cells. Conversely, EPO-dependent erythroid differentiation was inhibited by GATA-2 activation. These biological effects were obtained with levels of exogenous GATA-2 representing less than twofold increases over endogenous GATA-2 levels and were not observed in cells overexpressing GATA-1/ER. Similar effects on proliferation and differentiation were also observed in primary progenitor cells, freshly isolated from murine bone marrow and transduced with a GATA-2/ER-containing retrovirus. Taken together, these data suggest that threshold activities of GATA-2 in hematopoietic progenitor cells are a critical determinant in influencing self-renewal versus differentiation outcomes.

Indexed as

AnimalsBase SequenceCell DifferentiationCell LineCell LineageDNA-Binding ProteinsDNA PrimersErythroid-Specific DNA-Binding FactorsGATA1 Transcription FactorGATA2 Transcription FactorGene Expression Regulation, DevelopmentalLigandsMiceReceptors, EstrogenRecombinant Fusion ProteinsTranscription FactorsDNA-Binding ProteinsDNA PrimersErythroid-Specific DNA-Binding FactorsGata1 protein, mouseGATA1 Transcription FactorGata2 protein, mouseGATA2 Transcription FactorLigandsReceptors, EstrogenRecombinant Fusion ProteinsTranscription Factors

Identifiers

PMID10421636
PMCPMC316885
OpenAlexW2074675007

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.