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

Overview of attention for article published in BMC Genomics, October 2016
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  • Good Attention Score compared to outputs of the same age (66th percentile)
  • Good Attention Score compared to outputs of the same age and source (73rd percentile)

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Title
Distinct gene expression program dynamics during erythropoiesis from human induced pluripotent stem cells compared with adult and cord blood progenitors
Published in
BMC Genomics, October 2016
DOI 10.1186/s12864-016-3134-z
Pubmed ID
Authors

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

Human-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. Our 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. Together, 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.

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X Demographics

The data shown below were collected from the profiles of 9 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
Unknown 46 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 28%
Student > Ph. D. Student 10 21%
Other 6 13%
Student > Bachelor 3 6%
Student > Master 3 6%
Other 6 13%
Unknown 6 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 22 47%
Agricultural and Biological Sciences 7 15%
Medicine and Dentistry 3 6%
Engineering 3 6%
Arts and Humanities 1 2%
Other 4 9%
Unknown 7 15%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 September 2017.
All research outputs
#6,820,055
of 22,896,955 outputs
Outputs from BMC Genomics
#3,088
of 10,670 outputs
Outputs of similar age
#103,397
of 316,323 outputs
Outputs of similar age from BMC Genomics
#61
of 226 outputs
Altmetric has tracked 22,896,955 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 10,670 research outputs from this source. They receive a mean Attention Score of 4.7. This one has gotten more attention than average, scoring higher than 70% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 316,323 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.
We're also able to compare this research output to 226 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.