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Induced pluripotent stem cell models of Zellweger spectrum disorder show impaired peroxisome assembly and cell type-specific lipid abnormalities

Overview of attention for article published in Stem Cell Research & Therapy, August 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (84th percentile)
  • High Attention Score compared to outputs of the same age and source (91st percentile)

Mentioned by

news
1 news outlet
twitter
1 tweeter

Citations

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10 Dimensions

Readers on

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56 Mendeley
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Title
Induced pluripotent stem cell models of Zellweger spectrum disorder show impaired peroxisome assembly and cell type-specific lipid abnormalities
Published in
Stem Cell Research & Therapy, August 2015
DOI 10.1186/s13287-015-0149-3
Pubmed ID
Authors

Xiao-Ming Wang, Wing Yan Yik, Peilin Zhang, Wange Lu, Ning Huang, Bo Ram Kim, Darryl Shibata, Madison Zitting, Robert H. Chow, Ann B. Moser, Steven J. Steinberg, Joseph G. Hacia

Abstract

Zellweger spectrum disorder (PBD-ZSD) is a disease continuum caused by mutations in a subset of PEX genes required for normal peroxisome assembly and function. They highlight the importance of peroxisomes in the development and functions of the central nervous system, liver, and other organs. To date, the underlying bases for the cell-type specificity of disease are not fully elucidated. Primary skin fibroblasts from seven PBD-ZSD patients with biallelic PEX1, PEX10, PEX12, or PEX26 mutations and three healthy donors were transduced with retroviral vectors expressing Yamanaka reprogramming factors. Candidate induced pluripotent stem cells (iPSCs) were subject to global gene expression, DNA methylation, copy number variation, genotyping, in vitro differentiation and teratoma formation assays. Confirmed iPSCs were differentiated into neural progenitor cells (NPCs), neurons, oligodendrocyte precursor cells (OPCs), and hepatocyte-like cell cultures with peroxisome assembly evaluated by microscopy. Saturated very long chain fatty acid (sVLCFA) and plasmalogen levels were determined in primary fibroblasts and their derivatives. iPSCs were derived from seven PBD-ZSD patient-derived fibroblasts with mild to severe peroxisome assembly defects. Although patient and control skin fibroblasts had similar gene expression profiles, genes related to mitochondrial functions and organelle cross-talk were differentially expressed among corresponding iPSCs. Mitochondrial DNA levels were consistent among patient and control fibroblasts, but varied among all iPSCs. Relative to matching controls, sVLCFA levels were elevated in patient-derived fibroblasts, reduced in patient-derived iPSCs, and not significantly different in patient-derived NPCs. All cell types derived from donors with biallelic null mutations in a PEX gene showed plasmalogen deficiencies. Reporter gene assays compatible with high content screening (HCS) indicated patient-derived OPC and hepatocyte-like cell cultures had impaired peroxisome assembly. Normal peroxisome activity levels are not required for cellular reprogramming of skin fibroblasts. Patient iPSC gene expression profiles were consistent with hypotheses highlighting the role of altered mitochondrial activities and organelle cross-talk in PBD-ZSD pathogenesis. sVLCFA abnormalities dramatically differed among patient cell types, similar to observations made in iPSC models of X-linked adrenoleukodystrophy. We propose that iPSCs could assist investigations into the cell type-specificity of peroxisomal activities, toxicology studies, and in HCS for targeted therapies for peroxisome-related disorders.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter 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 56 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Sweden 1 2%
Unknown 55 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 23%
Student > Bachelor 10 18%
Other 5 9%
Student > Ph. D. Student 5 9%
Student > Master 5 9%
Other 8 14%
Unknown 10 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 21 38%
Agricultural and Biological Sciences 7 13%
Neuroscience 5 9%
Medicine and Dentistry 5 9%
Pharmacology, Toxicology and Pharmaceutical Science 3 5%
Other 5 9%
Unknown 10 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. 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 16 October 2015.
All research outputs
#2,297,845
of 17,356,510 outputs
Outputs from Stem Cell Research & Therapy
#190
of 1,744 outputs
Outputs of similar age
#38,532
of 246,583 outputs
Outputs of similar age from Stem Cell Research & Therapy
#1
of 12 outputs
Altmetric has tracked 17,356,510 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,744 research outputs from this source. They receive a mean Attention Score of 4.9. This one has done well, scoring higher than 88% 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 246,583 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 84% of its contemporaries.
We're also able to compare this research output to 12 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 91% of its contemporaries.