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Single-cell RNA-seq reveals novel regulators of human embryonic stem cell differentiation to definitive endoderm

Overview of attention for article published in Genome Biology, August 2016
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (90th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (61st percentile)

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2 blogs
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Citations

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360 Dimensions

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423 Mendeley
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3 CiteULike
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Title
Single-cell RNA-seq reveals novel regulators of human embryonic stem cell differentiation to definitive endoderm
Published in
Genome Biology, August 2016
DOI 10.1186/s13059-016-1033-x
Pubmed ID
Authors

Li-Fang Chu, Ning Leng, Jue Zhang, Zhonggang Hou, Daniel Mamott, David T. Vereide, Jeea Choi, Christina Kendziorski, Ron Stewart, James A. Thomson

Abstract

Human pluripotent stem cells offer the best available model to study the underlying cellular and molecular mechanisms of human embryonic lineage specification. However, it is not fully understood how individual stem cells exit the pluripotent state and transition towards their respective progenitor states. Here, we analyze the transcriptomes of human embryonic stem cell-derived lineage-specific progenitors by single-cell RNA-sequencing (scRNA-seq). We identify a definitive endoderm (DE) transcriptomic signature that leads us to pinpoint a critical time window when DE differentiation is enhanced by hypoxia. The molecular mechanisms governing the emergence of DE are further examined by time course scRNA-seq experiments, employing two new statistical tools to identify stage-specific genes over time (SCPattern) and to reconstruct the differentiation trajectory from the pluripotent state through mesendoderm to DE (Wave-Crest). Importantly, presumptive DE cells can be detected during the transitory phase from Brachyury (T) (+) mesendoderm toward a CXCR4 (+) DE state. Novel regulators are identified within this time window and are functionally validated on a screening platform with a T-2A-EGFP knock-in reporter engineered by CRISPR/Cas9. Through loss-of-function and gain-of-function experiments, we demonstrate that KLF8 plays a pivotal role modulating mesendoderm to DE differentiation. We report the analysis of 1776 cells by scRNA-seq covering distinct human embryonic stem cell-derived progenitor states. By reconstructing a differentiation trajectory at single-cell resolution, novel regulators of the mesendoderm transition to DE are elucidated and validated. Our strategy of combining single-cell analysis and genetic approaches can be applied to uncover novel regulators governing cell fate decisions in a variety of systems.

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X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 423 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 2 <1%
United States 2 <1%
Sweden 2 <1%
France 1 <1%
Japan 1 <1%
United Kingdom 1 <1%
Unknown 414 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 92 22%
Student > Ph. D. Student 91 22%
Student > Bachelor 54 13%
Student > Master 37 9%
Student > Doctoral Student 22 5%
Other 50 12%
Unknown 77 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 141 33%
Agricultural and Biological Sciences 97 23%
Medicine and Dentistry 24 6%
Computer Science 22 5%
Engineering 13 3%
Other 38 9%
Unknown 88 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 19. 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 08 September 2016.
All research outputs
#1,932,645
of 25,374,647 outputs
Outputs from Genome Biology
#1,618
of 4,467 outputs
Outputs of similar age
#33,496
of 354,260 outputs
Outputs of similar age from Genome Biology
#23
of 59 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,467 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 27.6. This one has gotten more attention than average, scoring higher than 63% 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 354,260 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 90% of its contemporaries.
We're also able to compare this research output to 59 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 61% of its contemporaries.