Evidence map›Paper›PMID 27769165›Full record

ArticleBMC genomics2016

Distinct gene expression program dynamics during erythropoiesis from human induced pluripotent stem cells compared with adult and cord blood progenitors.

Alison T Merryweather-Clarke, Alex J Tipping, Abigail A Lamikanra, Rui Fa, Basel Abu-Jamous, Hoi Pat Tsang, Lee Carpenter, Kathryn J H Robson, Asoke K Nandi, David J Roberts

Abstract read
In one paragraph

Article in BMC genomics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Blood Pharming of Red Cells.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Analyses of erythropoiesis from embryonic stem cell-CD34Journal of cellular and molecular medicine · 2022
    Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
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

10 authors.

Alison T Merryweather-ClarkeRadcliffe Department of Medicine, University of Oxford, Headington, Oxford, OX3 9DU, UK.
Alex J TippingRadcliffe Department of Medicine, University of Oxford, Headington, Oxford, OX3 9DU, UK.
Abigail A LamikanraRadcliffe Department of Medicine, University of Oxford, Headington, Oxford, OX3 9DU, UK. abigail.lamikanra@ndcls.ox.ac.uk.
Rui FaDepartment of Electronic and Computer Engineering, Brunel University London, Middlesex, UB8 3PH, UK.
Basel Abu-JamousDepartment of Electronic and Computer Engineering, Brunel University London, Middlesex, UB8 3PH, UK.
Hoi Pat TsangRadcliffe Department of Medicine, University of Oxford, Headington, Oxford, OX3 9DU, UK.
Lee CarpenterRadcliffe Department of Medicine, University of Oxford, Headington, Oxford, OX3 9DU, UK.
Kathryn J H RobsonMRC Weatherall Institute of Molecular Medicine, University of Oxford, Headington, OX3 9DU, Oxford, UK.
Asoke K NandiDepartment of Electronic and Computer Engineering, Brunel University London, Middlesex, UB8 3PH, UK.
David J RobertsRadcliffe Department of Medicine, University of Oxford, Headington, Oxford, OX3 9DU, UK. david.roberts@ndcls.ox.ac.uk.

Funding

Department of Health RP-PG-0310-1003Department of Health RP-PG-0310-1004
6 · The paper itself

Abstract

backgroundHuman-induced pluripotent stem cells (hiPSCs) are a potentially invaluable resource for regenerative medicine, including the in vitro manufacture of blood products. HiPSC-derived red blood cells are an attractive therapeutic option in hematology, yet exhibit unexplained proliferation and enucleation defects that presently preclude such applications. We hypothesised that substantial differential regulation of gene expression during erythroid development accounts for these important differences between hiPSC-derived cells and those from adult or cord-blood progenitors. We thus cultured erythroblasts from each source for transcriptomic analysis to investigate differential gene expression underlying these functional defects.

resultsOur high resolution transcriptional view of definitive erythropoiesis captures the regulation of genes relevant to cell-cycle control and confers statistical power to deploy novel bioinformatics methods. Whilst the dynamics of erythroid program elaboration from adult and cord blood progenitors were very similar, the emerging erythroid transcriptome in hiPSCs revealed radically different program elaboration compared to adult and cord blood cells. We explored the function of differentially expressed genes in hiPSC-specific clusters defined by our novel tunable clustering algorithms (SMART and Bi-CoPaM). HiPSCs show reduced expression of c-KIT and key erythroid transcription factors SOX6, MYB and BCL11A, strong HBZ-induction, and aberrant expression of genes involved in protein degradation, lysosomal clearance and cell-cycle regulation.

conclusionsTogether, these data suggest that hiPSC-derived cells may be specified to a primitive erythroid fate, and implies that definitive specification may more accurately reflect adult development. We have therefore identified, for the first time, distinct gene expression dynamics during erythroblast differentiation from hiPSCs which may cause reduced proliferation and enucleation of hiPSC-derived erythroid cells. The data suggest several mechanistic defects which may partially explain the observed aberrant erythroid differentiation from hiPSCs.

Indexed as

Gene Expression Regulation, DevelopmentalTranscriptomeCell DifferentiationCluster AnalysisErythroblastsErythropoiesisFetal BloodGene Expression ProfilingHematopoietic Stem CellsHumansInduced Pluripotent Stem CellsErythropoiesishiPSCSMART and Bi-CoPaMTranscriptome

Identifiers

PMID27769165
PMCPMC5073849

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.