Evidence map›Paper›PMID 25107887›Full record

ArticleHaematologica2014

Induction of adult levels of β-globin in human erythroid cells that intrinsically express embryonic or fetal globin by transduction with KLF1 and BCL11A-XL.

Kongtana Trakarnsanga, Marieangela C Wilson, Winnie Lau, Belinda K Singleton, Steve F Parsons, Punthita Sakuntanaga, Ryo Kurita, Yukio Nakamura, David J Anstee, Jan Frayne

Open access · goldAbstract read
In one paragraph

Article in Haematologica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

40 citing papers in PubMed, 67 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 3 countries.

Kongtana TrakarnsangaSchool of Biochemistry, University of Bristol, Bristol, United Kingdom Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Marieangela C WilsonSchool of Biochemistry, University of Bristol, Bristol, United Kingdom.
Winnie LauSchool of Biochemistry, University of Bristol, Bristol, United Kingdom.
Belinda K SingletonBristol Institute for Transfusion Sciences, National Health Service Blood and Transplant (NHSBT), Filton, Bristol, UK.
Steve F ParsonsBristol Institute for Transfusion Sciences, National Health Service Blood and Transplant (NHSBT), Filton, Bristol, UK.
Punthita SakuntanagaSchool of Biochemistry, University of Bristol, Bristol, United Kingdom.
Ryo KuritaCell Engineering Division, RIKEN BioResource Center, Tsukuba, Ibaraki, Japan.
Yukio NakamuraCell Engineering Division, RIKEN BioResource Center, Tsukuba, Ibaraki, Japan.
David J AnsteeBristol Institute for Transfusion Sciences, National Health Service Blood and Transplant (NHSBT), Filton, Bristol, UK jan.frayne@bristol.ac.uk david.anstee@nhsbt.nhs.uk.
Jan FrayneSchool of Biochemistry, University of Bristol, Bristol, United Kingdom jan.frayne@bristol.ac.uk david.anstee@nhsbt.nhs.uk.
University of Bristol · GBNational Health Service · GBRIKEN BioResource Research Center · JPNHS Blood and Transplant · GB

Funding

Department of Health RP-PG-0310-1004
6 · The paper itself

Abstract

A major barrier to the clinical use of erythrocytes generated in vitro from pluripotent stem cells or cord blood progenitors is failure of these erythrocytes to express adult hemoglobin. The key regulators of globin switching KLF1 and BCL11A are absent or at a lower level than in adult cells in K562 and erythroid cells differentiated in vitro from induced pluripotent stem cells and cord blood progenitors. Transfection or transduction of K562 and cord blood erythroid cells with either KLF1 or BCL11A-XL had little effect on β-globin expression. In contrast, transduction with both transcription factors stimulated β-globin expression. Similarly, increasing the level of BCL11A-XL in the induced pluripotent stem cell-derived erythroid cell line HiDEP-1, which has levels of endogenous KLF1 similar to adult cells but lacks BCL11A, resulted in levels of β-globin equivalent to that of adult erythroid cells. Interestingly, this increase in β-globin was coincident with a decrease in ε- and ζ-, but not γ-globin, implicating BCL11A in repression of embryonic globin expression. The data show that KLF1 and BCL11A-XL together are required, but sufficient to induce adult levels of β-globin in induced pluripotent stem cell and cord blood-derived erythroid cells that intrinsically express embryonic or fetal globin.

Indexed as

Gene ExpressionTransduction, GeneticAdult Stem Cellsbeta-GlobinsCarrier ProteinsCell DifferentiationCell Lineepsilon-GlobinsErythroid CellsFetal Hemoglobingamma-GlobinsHematopoietic Stem CellsHumansInduced Pluripotent Stem CellsK562 CellsKruppel-Like Transcription FactorsBCL11A protein, humanbeta-GlobinsCarrier Proteinsepsilon-Globinserythroid Kruppel-like factorFetal Hemoglobingamma-GlobinsKruppel-Like Transcription FactorsNuclear ProteinsRepressor Proteins

Identifiers

PMID25107887
PMCPMC4222483
OpenAlexW2140632026

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.