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ECM-Dependent HIF Induction Directs Trophoblast Stem Cell Fate via LIMK1-Mediated Cytoskeletal Rearrangement

Overview of attention for article published in PLOS ONE, February 2013
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Title
ECM-Dependent HIF Induction Directs Trophoblast Stem Cell Fate via LIMK1-Mediated Cytoskeletal Rearrangement
Published in
PLOS ONE, February 2013
DOI 10.1371/journal.pone.0056949
Pubmed ID
Authors

Hwa J. Choi, Timothy A. Sanders, Kathryn V. Tormos, Kurosh Ameri, Justin D. Tsai, Angela M. Park, Julissa Gonzalez, Anthony M. Rajah, Xiaowei Liu, Diana M. Quinonez, Paolo F. Rinaudo, Emin Maltepe

Abstract

The Hypoxia-inducible Factor (HIF) family of transcriptional regulators coordinates the expression of dozens of genes in response to oxygen deprivation. Mammalian development occurs in a hypoxic environment and HIF-null mice therefore die in utero due to multiple embryonic and placental defects. Mouse embryonic stem cells do not differentiate into placental cells; therefore, trophoblast stem cells (TSCs) are used to study mouse placental development. Consistent with a requirement for HIF activity during placental development in utero, TSCs derived from HIF-null mice exhibit severe differentiation defects and fail to form trophoblast giant cells (TGCs) in vitro. Interestingly, differentiating TSCs induce HIF activity independent of oxygen tension via unclear mechanisms. Here, we show that altering the extracellular matrix (ECM) composition upon which TSCs are cultured changes their differentiation potential from TGCs to multinucleated syncytiotropholasts (SynTs) and blocks oxygen-independent HIF induction. We further find that modulation of Mitogen Activated Protein Kinase Kinase-1/2 (MAP2K1/2, MEK-1/2) signaling by ECM composition is responsible for this effect. In the absence of ECM-dependent cues, hypoxia-signaling pathways activate this MAPK cascade to drive HIF induction and redirect TSC fate along the TGC lineage. In addition, we show that integrity of the microtubule and actin cytoskeleton is critical for TGC fate determination. HIF-2α ensures TSC cytoskeletal integrity and promotes invasive TGC formation by interacting with c-MYC to induce non-canonical expression of Lim domain kinase 1-an enzyme that regulates microtubule and actin stability, as well as cell invasion. Thus, we find that HIF can integrate positional and metabolic cues from within the TSC niche to regulate placental development by modulating the cellular cytoskeleton via non-canonical gene expression.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 54 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Portugal 1 2%
Unknown 52 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 13 24%
Researcher 7 13%
Student > Bachelor 6 11%
Student > Master 4 7%
Student > Postgraduate 2 4%
Other 6 11%
Unknown 16 30%
Readers by discipline Count As %
Agricultural and Biological Sciences 15 28%
Biochemistry, Genetics and Molecular Biology 9 17%
Chemical Engineering 3 6%
Unspecified 1 2%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Other 6 11%
Unknown 19 35%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 07 March 2013.
All research outputs
#18,331,227
of 22,699,621 outputs
Outputs from PLOS ONE
#154,048
of 193,796 outputs
Outputs of similar age
#146,789
of 192,994 outputs
Outputs of similar age from PLOS ONE
#3,959
of 5,380 outputs
Altmetric has tracked 22,699,621 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 193,796 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.0. This one is in the 10th percentile – i.e., 10% of its peers scored the same or lower than it.
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 192,994 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 5,380 others from the same source and published within six weeks on either side of this one. This one is in the 17th percentile – i.e., 17% of its contemporaries scored the same or lower than it.