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Self-Renewal of Single Mouse Hematopoietic Stem Cells Is Reduced by JAK2V617F Without Compromising Progenitor Cell Expansion

Overview of attention for article published in PLoS Biology, June 2013
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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 (94th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (59th percentile)

Mentioned by

news
3 news outlets
twitter
6 tweeters

Citations

dimensions_citation
66 Dimensions

Readers on

mendeley
106 Mendeley
Title
Self-Renewal of Single Mouse Hematopoietic Stem Cells Is Reduced by JAK2V617F Without Compromising Progenitor Cell Expansion
Published in
PLoS Biology, June 2013
DOI 10.1371/journal.pbio.1001576
Pubmed ID
Authors

David G. Kent, Juan Li, Hinal Tanna, Juergen Fink, Kristina Kirschner, Dean C. Pask, Yvonne Silber, Tina L. Hamilton, Rachel Sneade, Benjamin D. Simons, Anthony R. Green

Abstract

Recent descriptions of significant heterogeneity in normal stem cells and cancers have altered our understanding of tumorigenesis, emphasizing the need to understand how single stem cells are subverted to cause tumors. Human myeloproliferative neoplasms (MPNs) are thought to reflect transformation of a hematopoietic stem cell (HSC) and the majority harbor an acquired V617F mutation in the JAK2 tyrosine kinase, making them a paradigm for studying the early stages of tumor establishment and progression. The consequences of activating tyrosine kinase mutations for stem and progenitor cell behavior are unclear. In this article, we identify a distinct cellular mechanism operative in stem cells. By using conditional knock-in mice, we show that the HSC defect resulting from expression of heterozygous human JAK2V617F is both quantitative (reduced HSC numbers) and qualitative (lineage biases and reduced self-renewal per HSC). The defect is intrinsic to individual HSCs and their progeny are skewed toward proliferation and differentiation as evidenced by single cell and transplantation assays. Aged JAK2V617F show a more pronounced defect as assessed by transplantation, but mice that transform reacquire competitive self-renewal ability. Quantitative analysis of HSC-derived clones was used to model the fate choices of normal and JAK2-mutant HSCs and indicates that JAK2V617F reduces self-renewal of individual HSCs but leaves progenitor expansion intact. This conclusion is supported by paired daughter cell analyses, which indicate that JAK2-mutant HSCs more often give rise to two differentiated daughter cells. Together these data suggest that acquisition of JAK2V617F alone is insufficient for clonal expansion and disease progression and causes eventual HSC exhaustion. Moreover, our results show that clonal expansion of progenitor cells provides a window in which collaborating mutations can accumulate to drive disease progression. Characterizing the mechanism(s) of JAK2V617F subclinical clonal expansions and the transition to overt MPNs will illuminate the earliest stages of tumor establishment and subclone competition, fundamentally shifting the way we treat and manage cancers.

Twitter Demographics

The data shown below were collected from the profiles of 6 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 106 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 2 2%
United States 1 <1%
France 1 <1%
Germany 1 <1%
Unknown 101 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 34 32%
Researcher 30 28%
Student > Master 10 9%
Student > Bachelor 10 9%
Other 7 7%
Other 7 7%
Unknown 8 8%
Readers by discipline Count As %
Agricultural and Biological Sciences 33 31%
Biochemistry, Genetics and Molecular Biology 28 26%
Medicine and Dentistry 15 14%
Mathematics 4 4%
Physics and Astronomy 2 2%
Other 10 9%
Unknown 14 13%

Attention Score in Context

This research output has an Altmetric Attention Score of 28. 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 14 August 2021.
All research outputs
#1,076,572
of 21,346,872 outputs
Outputs from PLoS Biology
#1,884
of 5,732 outputs
Outputs of similar age
#9,086
of 175,183 outputs
Outputs of similar age from PLoS Biology
#29
of 69 outputs
Altmetric has tracked 21,346,872 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,732 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 56.8. This one has gotten more attention than average, scoring higher than 67% 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 175,183 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 94% of its contemporaries.
We're also able to compare this research output to 69 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 59% of its contemporaries.