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Genome organization and chromatin analysis identify transcriptional downregulation of insulin-like growth factor signaling as a hallmark of aging in developing B cells

Overview of attention for article published in Genome Biology, September 2018
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (95th percentile)
  • High Attention Score compared to outputs of the same age and source (90th percentile)

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1 blog
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31 Dimensions

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72 Mendeley
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Title
Genome organization and chromatin analysis identify transcriptional downregulation of insulin-like growth factor signaling as a hallmark of aging in developing B cells
Published in
Genome Biology, September 2018
DOI 10.1186/s13059-018-1489-y
Pubmed ID
Authors

Hashem Koohy, Daniel J. Bolland, Louise S. Matheson, Stefan Schoenfelder, Claudia Stellato, Andrew Dimond, Csilla Várnai, Peter Chovanec, Tamara Chessa, Jeremy Denizot, Raquel Manzano Garcia, Steven W. Wingett, Paula Freire-Pritchett, Takashi Nagano, Phillip Hawkins, Len Stephens, Sarah Elderkin, Mikhail Spivakov, Peter Fraser, Anne E. Corcoran, Patrick D. Varga-Weisz

Abstract

Aging is characterized by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of aging on B cell development, we profiled gene expression and chromatin features genome-wide, including histone modifications and chromosome conformation, in bone marrow pro-B and pre-B cells from young and aged mice. Our analysis reveals that the expression levels of most genes are generally preserved in B cell precursors isolated from aged compared with young mice. Nonetheless, age-specific expression changes are observed at numerous genes, including microRNA encoding genes. Importantly, these changes are underpinned by multi-layered alterations in chromatin structure, including chromatin accessibility, histone modifications, long-range promoter interactions, and nuclear compartmentalization. Previous work has shown that differentiation is linked to changes in promoter-regulatory element interactions. We find that aging in B cell precursors is accompanied by rewiring of such interactions. We identify transcriptional downregulation of components of the insulin-like growth factor signaling pathway, in particular downregulation of Irs1 and upregulation of Let-7 microRNA expression, as a signature of the aged phenotype. These changes in expression are associated with specific alterations in H3K27me3 occupancy, suggesting that Polycomb-mediated repression plays a role in precursor B cell aging. Changes in chromatin and 3D genome organization play an important role in shaping the altered gene expression profile of aged precursor B cells. Components of the insulin-like growth factor signaling pathways are key targets of epigenetic regulation in aging in bone marrow B cell precursors.

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X Demographics

The data shown below were collected from the profiles of 90 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 72 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 72 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 20 28%
Researcher 15 21%
Other 6 8%
Student > Bachelor 4 6%
Student > Master 4 6%
Other 7 10%
Unknown 16 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 23 32%
Agricultural and Biological Sciences 13 18%
Immunology and Microbiology 7 10%
Medicine and Dentistry 5 7%
Computer Science 1 1%
Other 1 1%
Unknown 22 31%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 63. 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 24 January 2019.
All research outputs
#680,754
of 25,385,509 outputs
Outputs from Genome Biology
#433
of 4,468 outputs
Outputs of similar age
#14,578
of 345,354 outputs
Outputs of similar age from Genome Biology
#7
of 75 outputs
Altmetric has tracked 25,385,509 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,468 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 done particularly well, scoring higher than 90% 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 345,354 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 95% of its contemporaries.
We're also able to compare this research output to 75 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 90% of its contemporaries.